8kct

Cryo-EM structure of human gamma-secretase in complex with Nirogacestat

Method: ELECTRON MICROSCOPY D_max: 135.4 Å Quality: GOOD

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1. Protein Identity and Related Structures Protein Identity & Related Structures

Nicastrin

Homo sapiens

State in the Current Structure

Assembly	Oligomeric State	Construct	Mutations and Modifications	Ligands, Ions and Associated Components	Method and Experimental Conditions	Structure Quality
1	Other combination Heteromer Protein × 4 其他Polymer 6 PDB declaration: tetrameric（4） Consistent with protein copy count	Chain A； UniProt 1–701	Not recorded	Gamma-secretase subunit APH-1A × 1 （Q96BI3） Gamma-secretase subunit PEN-2 × 1 （Q9NZ42） Presenilin-1 × 1 （P49768） 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose × 5 ;beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose ; × 1 NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 CLR CHOLESTEROL × 3 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 O6U Nirogacestat × 1	ELECTRON MICROSCOPY cryo-EM buffer：pH 7.4 cryo-EM vitrification conditions：Cryogen ETHANE	Resolution 2.60 Å

Other States of the Same Protein in the Database

Each row is a biological assembly of the same UniProt protein in another PDB entry. The “Difference from current entry” column identifies evidence-level differences; no tag means the currently parsed fields agree.

Other PDB	Difference from Current Entry 8KCT	Assembly / Oligomeric State	Construct	Mutations and Modifications	Ligands, Ions and Non-polymers	Method and Experimental Conditions	Structure Quality
2N7Q Structure of the transmembrane domain of human nicastrin in SDS micelles Deposited 2015-09-17	Different construct Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 664–709（46 aa） Fragment：UNP residues 664-709	Not recorded	No recorded non-water small molecule	SOLUTION NMR NMR measurement conditions pH 6.5；313 K；Ionic strength (raw mmCIF value) 20；Pressure ambient NMR sample composition 0.8 mM [U-100% 13C; U-100% 15N] transmembrane domain of human nicastrin-1, 20 mM sodium phosphate-2, 100 mM SDS-3, 1 mM DTT-4, 90% H2O/10% D2O \| 90% H2O/10% D2O	Resolution not provided
2N7R Structure of the transmembrane domain of human nicastrin in DPC micelles Deposited 2015-09-17	Different construct Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 664–709（46 aa） Fragment：UNP residues 664-709	Not recorded	No recorded non-water small molecule	SOLUTION NMR NMR measurement conditions pH 6.5；313 K；Ionic strength (raw mmCIF value) 20；Pressure ambient NMR sample composition 0.8 mM [U-100% 13C; U-100% 15N] transmembrane domain of human nicastrin-1, 20 mM sodium phosphate-2, 200 mM DPC-3, 1 mM DTT-4, 90% H2O/10% D2O \| 90% H2O/10% D2O	Resolution not provided
5A63 Cryo-EM structure of the human gamma-secretase complex at 3.4 angstrom resolution. Deposited 2015-06-24	Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 5 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；VITRIFICATION 1 -- CRYOGEN- ETHANE, HUMIDITY- 100, TEMPERATURE- 85, INSTRUMENT- FEI VITROBOT MARK IV, METHOD- BLOT FOR 4 SECONDS BEFORE PLUNGING,	Resolution 3.40 Å
5FN2 Cryo-EM structure of gamma secretase in complex with a drug DAPT Deposited 2015-11-10	Different construct Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–709（709 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；LIQUID ETHANE	Resolution 4.20 Å
5FN3 Cryo-EM structure of gamma secretase in class 1 of the apo- state ensemble Deposited 2015-11-10	Different construct Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 5 PDB declaration: pentameric	Chain A 1–709（709 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；LIQUID ETHANE	Resolution 4.10 Å
5FN4 Cryo-EM structure of gamma secretase in class 2 of the apo- state ensemble Deposited 2015-11-10	Different construct Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 5 PDB declaration: pentameric	Chain A 1–709（709 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；LIQUID ETHANE	Resolution 4.00 Å
5FN5 Cryo-EM structure of gamma secretase in class 3 of the apo- state ensemble Deposited 2015-11-10	Different construct Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–709（709 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；LIQUID ETHANE	Resolution 4.30 Å
6IDF Cryo-EM structure of gamma secretase in complex with a Notch fragment Deposited 2018-09-09	Different construct Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 4 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.70 Å
6IYC Recognition of the Amyloid Precursor Protein by Human gamma-secretase Deposited 2018-12-14	Different construct Different oligomeric state Different ligand/ion	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.60 Å
6LQG Human gamma-secretase in complex with small molecule Avagacestat Deposited 2020-01-13	Different construct Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 EN9 (2R)-2-[(4-chlorophenyl)sulfonyl-[[2-fluoranyl-4-(1,2,4-oxadiazol-3-yl)phenyl]methyl]amino]-5,5,5-tris(fluoranyl)pentanamide × 1 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.10 Å
6LR4 Molecular basis for inhibition of human gamma-secretase by small molecule Deposited 2020-01-15	Different construct Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 ESF (2S)-2-hydroxy-3-methyl-N-[(2S)-1-[[(5S)-3-methyl-4-oxo-2,5-dihydro-1H-3-benzazepin-5-yl]amino]-1-oxopropan-2-yl]butanamide × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.00 Å
7C9I Human gamma-secretase in complex with small molecule L-685,458 Deposited 2020-06-05	Different construct Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 FTO ~{tert}-butyl ~{N}-[(2~{S},3~{R},5~{R})-6-[[(2~{S})-1-[[(2~{S})-1-azanyl-1-oxidanylidene-3-phenyl-propan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]amino]-3-oxidanyl-6-oxidanylidene-1-phenyl-5-(phenylmethyl)hexan-2-yl]carbamate × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.10 Å
7D8X CryoEM structure of human gamma-secretase in complex with E2012 and L685458 Deposited 2020-10-11	Different construct Different ligand/ion	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 GZR 1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylidene]piperidin-2-one × 1 PTY PHOSPHATIDYLETHANOLAMINE × 1 FTO ~{tert}-butyl ~{N}-[(2~{S},3~{R},5~{R})-6-[[(2~{S})-1-[[(2~{S})-1-azanyl-1-oxidanylidene-3-phenyl-propan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]amino]-3-oxidanyl-6-oxidanylidene-1-phenyl-5-(phenylmethyl)hexan-2-yl]carbamate × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.60 Å
7Y5T CryoEM structure of PS1-containing gamma-secretase in complex with MRK-560 Deposited 2022-06-17	Different construct Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 IGD ~{N}-[4-[2,5-bis(fluoranyl)phenyl]-4-(4-chlorophenyl)sulfonyl-cyclohexyl]-1,1,1-tris(fluoranyl)methanesulfonamide × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å
7Y5X CryoEM structure of PS2-containing gamma-secretase treated with MRK-560 Deposited 2022-06-17	Different construct Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.00 Å
7Y5Z CryoEM structure of human PS2-containing gamma-secretase Deposited 2022-06-18	Different construct Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.40 Å
8IM7 Human gamma-secretase treated with ganglioside GM1 Deposited 2023-03-06	Different construct Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.40 Å
8K8E Human gamma-secretase in complex with a substrate mimetic Deposited 2023-07-29	Different construct Different oligomeric state Different ligand/ion	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.60 Å
8KCO Cryo-EM structure of human gamma-secretase in complex with RO4929097 Deposited 2023-08-08	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–701（701 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 N60 2,2-dimethyl-N-[(7S)-6-oxo-5,7-dihydrobenzo[d][1]benzazepin-7-yl]-N'-(2,2,3,3,3-pentafluoropropyl)propanediamide × 1 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.80 Å
8KCP Cryo-EM structure of human gamma-secretase in complex with Crenigacestat Deposited 2023-08-08	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–701（701 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 N9C 4,4,4-tris(fluoranyl)-N-[(2S)-1-[[(7S)-5-(2-hydroxyethyl)-6-oxidanylidene-7H-pyrido[2,3-d][3]benzazepin-7-yl]amino]-1-oxidanylidene-propan-2-yl]butanamide × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.00 Å
8KCS Cryo-EM structure of human gamma-secretase in complex with BMS906024 Deposited 2023-08-08	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–701（701 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 Q70 Osugacestat × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.40 Å
8KCU Cryo-EM structure of human gamma-secretase in complex with MK-0752 Deposited 2023-08-08	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–701（701 aa）	Not recorded	PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 OL9 MK-0752 × 1 NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.70 Å
8OQY Structure of apo form of human gamma-secretase PSEN1 APH-1B isoform reconstituted into lipid nanodisc Deposited 2023-04-12	Different construct Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 7 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.30 Å
8OQZ Structure of human gamma-secretase PSEN1 APH-1B isoform reconstituted into lipid nanodisc in complex with Ab46 Deposited 2023-04-12	Different construct Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 8 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 14	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.40 Å
8X52 Cryo-EM structure of human gamma-secretase in complex with Abeta49 Deposited 2023-11-16	Different construct Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å
8X53 Cryo-EM structure of human gamma-secretase in complex with Abeta46 Deposited 2023-11-16	Different construct Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 3 CLR CHOLESTEROL × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.00 Å
8X54 Cryo-EM structure of human gamma-secretase in complex with APP-C99 Deposited 2023-11-16	Different construct Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 3 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å
9K95 Cryo-EM structure of human gamma-secretase in complex with compound E Deposited 2024-10-25	Different construct Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–709（709 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 A1D6X (2~{S})-2-[2-[3,5-bis(fluoranyl)phenyl]ethanoylamino]-~{N}-[(3~{S})-1-methyl-2-oxidanylidene-5-phenyl-3~{H}-1,4-benzodiazepin-3-yl]propanamide × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å

28 other PDB entries and 28 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence

UniProt name	NICA_HUMAN
Isoform	—
PDB entities	1
Chains and sequence ranges	Author chain A； PDBConstruct 1–701； UniProt 1–701

Gamma-secretase subunit APH-1A

Homo sapiens

UniProt Q96BI3

State in the Current Structure

Assembly	Oligomeric State	Construct	Mutations and Modifications	Ligands, Ions and Associated Components	Method and Experimental Conditions	Structure Quality
1	Other combination Heteromer Protein × 4 其他Polymer 6 PDB declaration: tetrameric（4） Consistent with protein copy count	Chain C； UniProt 1–265	Not recorded	Nicastrin × 1 （Q92542） Gamma-secretase subunit PEN-2 × 1 （Q9NZ42） Presenilin-1 × 1 （P49768） 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose × 5 ;beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose ; × 1 NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 CLR CHOLESTEROL × 3 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 O6U Nirogacestat × 1	ELECTRON MICROSCOPY cryo-EM buffer：pH 7.4 cryo-EM vitrification conditions：Cryogen ETHANE	Resolution 2.60 Å

Other States of the Same Protein in the Database

Other PDB	Difference from Current Entry 8KCT	Assembly / Oligomeric State	Construct	Mutations and Modifications	Ligands, Ions and Non-polymers	Method and Experimental Conditions	Structure Quality
5A63 Cryo-EM structure of the human gamma-secretase complex at 3.4 angstrom resolution. Deposited 2015-06-24	Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 5 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；VITRIFICATION 1 -- CRYOGEN- ETHANE, HUMIDITY- 100, TEMPERATURE- 85, INSTRUMENT- FEI VITROBOT MARK IV, METHOD- BLOT FOR 4 SECONDS BEFORE PLUNGING,	Resolution 3.40 Å
5FN2 Cryo-EM structure of gamma secretase in complex with a drug DAPT Deposited 2015-11-10	Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–265（265 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；LIQUID ETHANE	Resolution 4.20 Å
5FN3 Cryo-EM structure of gamma secretase in class 1 of the apo- state ensemble Deposited 2015-11-10	Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 5 PDB declaration: pentameric	Chain C 1–265（265 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；LIQUID ETHANE	Resolution 4.10 Å
5FN4 Cryo-EM structure of gamma secretase in class 2 of the apo- state ensemble Deposited 2015-11-10	Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 5 PDB declaration: pentameric	Chain C 1–265（265 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；LIQUID ETHANE	Resolution 4.00 Å
5FN5 Cryo-EM structure of gamma secretase in class 3 of the apo- state ensemble Deposited 2015-11-10	Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–265（265 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；LIQUID ETHANE	Resolution 4.30 Å
6IDF Cryo-EM structure of gamma secretase in complex with a Notch fragment Deposited 2018-09-09	Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 4 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.70 Å
6IYC Recognition of the Amyloid Precursor Protein by Human gamma-secretase Deposited 2018-12-14	Different oligomeric state Different ligand/ion	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.60 Å
6LQG Human gamma-secretase in complex with small molecule Avagacestat Deposited 2020-01-13	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 EN9 (2R)-2-[(4-chlorophenyl)sulfonyl-[[2-fluoranyl-4-(1,2,4-oxadiazol-3-yl)phenyl]methyl]amino]-5,5,5-tris(fluoranyl)pentanamide × 1 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.10 Å
6LR4 Molecular basis for inhibition of human gamma-secretase by small molecule Deposited 2020-01-15	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 ESF (2S)-2-hydroxy-3-methyl-N-[(2S)-1-[[(5S)-3-methyl-4-oxo-2,5-dihydro-1H-3-benzazepin-5-yl]amino]-1-oxopropan-2-yl]butanamide × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.00 Å
7C9I Human gamma-secretase in complex with small molecule L-685,458 Deposited 2020-06-05	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 FTO ~{tert}-butyl ~{N}-[(2~{S},3~{R},5~{R})-6-[[(2~{S})-1-[[(2~{S})-1-azanyl-1-oxidanylidene-3-phenyl-propan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]amino]-3-oxidanyl-6-oxidanylidene-1-phenyl-5-(phenylmethyl)hexan-2-yl]carbamate × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.10 Å
7D8X CryoEM structure of human gamma-secretase in complex with E2012 and L685458 Deposited 2020-10-11	Different ligand/ion	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 GZR 1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylidene]piperidin-2-one × 1 PTY PHOSPHATIDYLETHANOLAMINE × 1 FTO ~{tert}-butyl ~{N}-[(2~{S},3~{R},5~{R})-6-[[(2~{S})-1-[[(2~{S})-1-azanyl-1-oxidanylidene-3-phenyl-propan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]amino]-3-oxidanyl-6-oxidanylidene-1-phenyl-5-(phenylmethyl)hexan-2-yl]carbamate × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.60 Å
7Y5T CryoEM structure of PS1-containing gamma-secretase in complex with MRK-560 Deposited 2022-06-17	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 IGD ~{N}-[4-[2,5-bis(fluoranyl)phenyl]-4-(4-chlorophenyl)sulfonyl-cyclohexyl]-1,1,1-tris(fluoranyl)methanesulfonamide × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å
7Y5X CryoEM structure of PS2-containing gamma-secretase treated with MRK-560 Deposited 2022-06-17	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.00 Å
7Y5Z CryoEM structure of human PS2-containing gamma-secretase Deposited 2022-06-18	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.40 Å
8IM7 Human gamma-secretase treated with ganglioside GM1 Deposited 2023-03-06	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.40 Å
8K8E Human gamma-secretase in complex with a substrate mimetic Deposited 2023-07-29	Different oligomeric state Different ligand/ion	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.60 Å
8KCO Cryo-EM structure of human gamma-secretase in complex with RO4929097 Deposited 2023-08-08	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 N60 2,2-dimethyl-N-[(7S)-6-oxo-5,7-dihydrobenzo[d][1]benzazepin-7-yl]-N'-(2,2,3,3,3-pentafluoropropyl)propanediamide × 1 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.80 Å
8KCP Cryo-EM structure of human gamma-secretase in complex with Crenigacestat Deposited 2023-08-08	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 N9C 4,4,4-tris(fluoranyl)-N-[(2S)-1-[[(7S)-5-(2-hydroxyethyl)-6-oxidanylidene-7H-pyrido[2,3-d][3]benzazepin-7-yl]amino]-1-oxidanylidene-propan-2-yl]butanamide × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.00 Å
8KCS Cryo-EM structure of human gamma-secretase in complex with BMS906024 Deposited 2023-08-08	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 Q70 Osugacestat × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.40 Å
8KCU Cryo-EM structure of human gamma-secretase in complex with MK-0752 Deposited 2023-08-08	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–265（265 aa）	Not recorded	PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 OL9 MK-0752 × 1 NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.70 Å
8X52 Cryo-EM structure of human gamma-secretase in complex with Abeta49 Deposited 2023-11-16	Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å
8X53 Cryo-EM structure of human gamma-secretase in complex with Abeta46 Deposited 2023-11-16	Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 3 CLR CHOLESTEROL × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.00 Å
8X54 Cryo-EM structure of human gamma-secretase in complex with APP-C99 Deposited 2023-11-16	Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 3 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å
9K95 Cryo-EM structure of human gamma-secretase in complex with compound E Deposited 2024-10-25	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–265（265 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 A1D6X (2~{S})-2-[2-[3,5-bis(fluoranyl)phenyl]ethanoylamino]-~{N}-[(3~{S})-1-methyl-2-oxidanylidene-5-phenyl-3~{H}-1,4-benzodiazepin-3-yl]propanamide × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å

24 other PDB entries and 24 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence

UniProt name	APH1A_HUMAN
Isoform	—
PDB entities	2
Chains and sequence ranges	Author chain C； PDBConstruct 1–265； UniProt 1–265

Gamma-secretase subunit PEN-2

Homo sapiens

UniProt Q9NZ42

State in the Current Structure

Assembly	Oligomeric State	Construct	Mutations and Modifications	Ligands, Ions and Associated Components	Method and Experimental Conditions	Structure Quality
1	Other combination Heteromer Protein × 4 其他Polymer 6 PDB declaration: tetrameric（4） Consistent with protein copy count	Chain D； UniProt 1–101	Not recorded	Nicastrin × 1 （Q92542） Gamma-secretase subunit APH-1A × 1 （Q96BI3） Presenilin-1 × 1 （P49768） 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose × 5 ;beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose ; × 1 NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 CLR CHOLESTEROL × 3 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 O6U Nirogacestat × 1	ELECTRON MICROSCOPY cryo-EM buffer：pH 7.4 cryo-EM vitrification conditions：Cryogen ETHANE	Resolution 2.60 Å

Other States of the Same Protein in the Database

Other PDB	Difference from Current Entry 8KCT	Assembly / Oligomeric State	Construct	Mutations and Modifications	Ligands, Ions and Non-polymers	Method and Experimental Conditions	Structure Quality
5A63 Cryo-EM structure of the human gamma-secretase complex at 3.4 angstrom resolution. Deposited 2015-06-24	Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 1–101（101 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 5 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；VITRIFICATION 1 -- CRYOGEN- ETHANE, HUMIDITY- 100, TEMPERATURE- 85, INSTRUMENT- FEI VITROBOT MARK IV, METHOD- BLOT FOR 4 SECONDS BEFORE PLUNGING,	Resolution 3.40 Å
5FN2 Cryo-EM structure of gamma secretase in complex with a drug DAPT Deposited 2015-11-10	Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 1–101（101 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；LIQUID ETHANE	Resolution 4.20 Å
5FN3 Cryo-EM structure of gamma secretase in class 1 of the apo- state ensemble Deposited 2015-11-10	Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 5 PDB declaration: pentameric	Chain D 1–101（101 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；LIQUID ETHANE	Resolution 4.10 Å
5FN4 Cryo-EM structure of gamma secretase in class 2 of the apo- state ensemble Deposited 2015-11-10	Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 5 PDB declaration: pentameric	Chain D 1–101（101 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；LIQUID ETHANE	Resolution 4.00 Å
5FN5 Cryo-EM structure of gamma secretase in class 3 of the apo- state ensemble Deposited 2015-11-10	Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 1–101（101 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；LIQUID ETHANE	Resolution 4.30 Å
6IDF Cryo-EM structure of gamma secretase in complex with a Notch fragment Deposited 2018-09-09	Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain D 1–101（101 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 4 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.70 Å
6IYC Recognition of the Amyloid Precursor Protein by Human gamma-secretase Deposited 2018-12-14	Different oligomeric state Different ligand/ion	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain D 1–101（101 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.60 Å
6LQG Human gamma-secretase in complex with small molecule Avagacestat Deposited 2020-01-13	Different construct Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 2–101（100 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 EN9 (2R)-2-[(4-chlorophenyl)sulfonyl-[[2-fluoranyl-4-(1,2,4-oxadiazol-3-yl)phenyl]methyl]amino]-5,5,5-tris(fluoranyl)pentanamide × 1 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.10 Å
6LR4 Molecular basis for inhibition of human gamma-secretase by small molecule Deposited 2020-01-15	Different construct Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 2–101（100 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 ESF (2S)-2-hydroxy-3-methyl-N-[(2S)-1-[[(5S)-3-methyl-4-oxo-2,5-dihydro-1H-3-benzazepin-5-yl]amino]-1-oxopropan-2-yl]butanamide × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.00 Å
7C9I Human gamma-secretase in complex with small molecule L-685,458 Deposited 2020-06-05	Different construct Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 2–101（100 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 FTO ~{tert}-butyl ~{N}-[(2~{S},3~{R},5~{R})-6-[[(2~{S})-1-[[(2~{S})-1-azanyl-1-oxidanylidene-3-phenyl-propan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]amino]-3-oxidanyl-6-oxidanylidene-1-phenyl-5-(phenylmethyl)hexan-2-yl]carbamate × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.10 Å
7D8X CryoEM structure of human gamma-secretase in complex with E2012 and L685458 Deposited 2020-10-11	Different construct Different ligand/ion	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 2–101（100 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 GZR 1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylidene]piperidin-2-one × 1 PTY PHOSPHATIDYLETHANOLAMINE × 1 FTO ~{tert}-butyl ~{N}-[(2~{S},3~{R},5~{R})-6-[[(2~{S})-1-[[(2~{S})-1-azanyl-1-oxidanylidene-3-phenyl-propan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]amino]-3-oxidanyl-6-oxidanylidene-1-phenyl-5-(phenylmethyl)hexan-2-yl]carbamate × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.60 Å
7Y5T CryoEM structure of PS1-containing gamma-secretase in complex with MRK-560 Deposited 2022-06-17	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 1–101（101 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 IGD ~{N}-[4-[2,5-bis(fluoranyl)phenyl]-4-(4-chlorophenyl)sulfonyl-cyclohexyl]-1,1,1-tris(fluoranyl)methanesulfonamide × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å
7Y5X CryoEM structure of PS2-containing gamma-secretase treated with MRK-560 Deposited 2022-06-17	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 1–101（101 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.00 Å
7Y5Z CryoEM structure of human PS2-containing gamma-secretase Deposited 2022-06-18	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 1–101（101 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.40 Å
8IM7 Human gamma-secretase treated with ganglioside GM1 Deposited 2023-03-06	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 1–101（101 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.40 Å
8K8E Human gamma-secretase in complex with a substrate mimetic Deposited 2023-07-29	Different oligomeric state Different ligand/ion	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain D 1–101（101 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.60 Å
8KCO Cryo-EM structure of human gamma-secretase in complex with RO4929097 Deposited 2023-08-08	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 1–101（101 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 N60 2,2-dimethyl-N-[(7S)-6-oxo-5,7-dihydrobenzo[d][1]benzazepin-7-yl]-N'-(2,2,3,3,3-pentafluoropropyl)propanediamide × 1 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.80 Å
8KCP Cryo-EM structure of human gamma-secretase in complex with Crenigacestat Deposited 2023-08-08	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 1–101（101 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 N9C 4,4,4-tris(fluoranyl)-N-[(2S)-1-[[(7S)-5-(2-hydroxyethyl)-6-oxidanylidene-7H-pyrido[2,3-d][3]benzazepin-7-yl]amino]-1-oxidanylidene-propan-2-yl]butanamide × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.00 Å
8KCS Cryo-EM structure of human gamma-secretase in complex with BMS906024 Deposited 2023-08-08	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 1–101（101 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 Q70 Osugacestat × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.40 Å
8KCU Cryo-EM structure of human gamma-secretase in complex with MK-0752 Deposited 2023-08-08	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 1–101（101 aa）	Not recorded	PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 OL9 MK-0752 × 1 NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.70 Å
8OQY Structure of apo form of human gamma-secretase PSEN1 APH-1B isoform reconstituted into lipid nanodisc Deposited 2023-04-12	Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 1–101（101 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 7 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.30 Å
8OQZ Structure of human gamma-secretase PSEN1 APH-1B isoform reconstituted into lipid nanodisc in complex with Ab46 Deposited 2023-04-12	Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain D 1–101（101 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 8 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 14	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.40 Å
8X52 Cryo-EM structure of human gamma-secretase in complex with Abeta49 Deposited 2023-11-16	Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain D 1–101（101 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å
8X53 Cryo-EM structure of human gamma-secretase in complex with Abeta46 Deposited 2023-11-16	Different construct Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain D 2–101（100 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 3 CLR CHOLESTEROL × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.00 Å
8X54 Cryo-EM structure of human gamma-secretase in complex with APP-C99 Deposited 2023-11-16	Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain D 1–101（101 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 3 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å
9K95 Cryo-EM structure of human gamma-secretase in complex with compound E Deposited 2024-10-25	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain D 1–101（101 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 A1D6X (2~{S})-2-[2-[3,5-bis(fluoranyl)phenyl]ethanoylamino]-~{N}-[(3~{S})-1-methyl-2-oxidanylidene-5-phenyl-3~{H}-1,4-benzodiazepin-3-yl]propanamide × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å

26 other PDB entries and 26 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence

UniProt name	PEN2_HUMAN
Isoform	—
PDB entities	3
Chains and sequence ranges	Author chain D； PDBConstruct 1–101； UniProt 1–101

Presenilin-1

Homo sapiens

UniProt P49768

State in the Current Structure

Assembly	Oligomeric State	Construct	Mutations and Modifications	Ligands, Ions and Associated Components	Method and Experimental Conditions	Structure Quality
1	Other combination Heteromer Protein × 4 其他Polymer 6 PDB declaration: tetrameric（4） Consistent with protein copy count	Chain B； UniProt 1–467	Not recorded	Nicastrin × 1 （Q92542） Gamma-secretase subunit APH-1A × 1 （Q96BI3） Gamma-secretase subunit PEN-2 × 1 （Q9NZ42） 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose × 5 ;beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose ; × 1 NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 CLR CHOLESTEROL × 3 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 O6U Nirogacestat × 1	ELECTRON MICROSCOPY cryo-EM buffer：pH 7.4 cryo-EM vitrification conditions：Cryogen ETHANE	Resolution 2.60 Å

Other States of the Same Protein in the Database

Other PDB	Difference from Current Entry 8KCT	Assembly / Oligomeric State	Construct	Mutations and Modifications	Ligands, Ions and Non-polymers	Method and Experimental Conditions	Structure Quality
2KR6 Solution structure of presenilin-1 CTF subunit Deposited 2009-12-04	Different construct Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 292–467（176 aa） Fragment：Presenilin-1 CTF subunit, UNP residues 292-467	Not recorded	No recorded non-water small molecule	SOLUTION NMR NMR measurement conditions pH 6.8；313 K；Ionic strength (raw mmCIF value) 20；Pressure AMBIENT NMR sample composition 0.5 mM [U-99% 13C; U-99% 15N] ps1ctf-1, 90% H2O/10% D2O \| 90% H2O/10% D2O	Resolution not provided
5A63 Cryo-EM structure of the human gamma-secretase complex at 3.4 angstrom resolution. Deposited 2015-06-24	Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 5 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；VITRIFICATION 1 -- CRYOGEN- ETHANE, HUMIDITY- 100, TEMPERATURE- 85, INSTRUMENT- FEI VITROBOT MARK IV, METHOD- BLOT FOR 4 SECONDS BEFORE PLUNGING,	Resolution 3.40 Å
5FN2 Cryo-EM structure of gamma secretase in complex with a drug DAPT Deposited 2015-11-10	Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric	Chain B 1–467（467 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；LIQUID ETHANE	Resolution 4.20 Å
5FN3 Cryo-EM structure of gamma secretase in class 1 of the apo- state ensemble Deposited 2015-11-10	Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 5 PDB declaration: pentameric	Chain B 1–467（467 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；LIQUID ETHANE	Resolution 4.10 Å
5FN4 Cryo-EM structure of gamma secretase in class 2 of the apo- state ensemble Deposited 2015-11-10	Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 5 PDB declaration: pentameric	Chain B 1–467（467 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；LIQUID ETHANE	Resolution 4.00 Å
5FN5 Cryo-EM structure of gamma secretase in class 3 of the apo- state ensemble Deposited 2015-11-10	Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric	Chain B 1–467（467 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer 25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35；pH 7.4；25 MM HEPES, PH 7.4, 150 MM NACL AND AMPHIPOL A8-35 cryo-EM vitrification conditions Cryogen ETHANE；LIQUID ETHANE	Resolution 4.30 Å
6IDF Cryo-EM structure of gamma secretase in complex with a Notch fragment Deposited 2018-09-09	Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 4 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.70 Å
6IYC Recognition of the Amyloid Precursor Protein by Human gamma-secretase Deposited 2018-12-14	Different mutation/modification Different oligomeric state Different ligand/ion	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain B 1–467（467 aa）	Mutation：Q112C	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.60 Å
6LQG Human gamma-secretase in complex with small molecule Avagacestat Deposited 2020-01-13	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 EN9 (2R)-2-[(4-chlorophenyl)sulfonyl-[[2-fluoranyl-4-(1,2,4-oxadiazol-3-yl)phenyl]methyl]amino]-5,5,5-tris(fluoranyl)pentanamide × 1 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.10 Å
6LR4 Molecular basis for inhibition of human gamma-secretase by small molecule Deposited 2020-01-15	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 ESF (2S)-2-hydroxy-3-methyl-N-[(2S)-1-[[(5S)-3-methyl-4-oxo-2,5-dihydro-1H-3-benzazepin-5-yl]amino]-1-oxopropan-2-yl]butanamide × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.00 Å
7C9I Human gamma-secretase in complex with small molecule L-685,458 Deposited 2020-06-05	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 FTO ~{tert}-butyl ~{N}-[(2~{S},3~{R},5~{R})-6-[[(2~{S})-1-[[(2~{S})-1-azanyl-1-oxidanylidene-3-phenyl-propan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]amino]-3-oxidanyl-6-oxidanylidene-1-phenyl-5-(phenylmethyl)hexan-2-yl]carbamate × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.10 Å
7D8X CryoEM structure of human gamma-secretase in complex with E2012 and L685458 Deposited 2020-10-11	Different ligand/ion	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 GZR 1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylidene]piperidin-2-one × 1 PTY PHOSPHATIDYLETHANOLAMINE × 1 FTO ~{tert}-butyl ~{N}-[(2~{S},3~{R},5~{R})-6-[[(2~{S})-1-[[(2~{S})-1-azanyl-1-oxidanylidene-3-phenyl-propan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]amino]-3-oxidanyl-6-oxidanylidene-1-phenyl-5-(phenylmethyl)hexan-2-yl]carbamate × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.60 Å
7Y5T CryoEM structure of PS1-containing gamma-secretase in complex with MRK-560 Deposited 2022-06-17	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 IGD ~{N}-[4-[2,5-bis(fluoranyl)phenyl]-4-(4-chlorophenyl)sulfonyl-cyclohexyl]-1,1,1-tris(fluoranyl)methanesulfonamide × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å
8IM7 Human gamma-secretase treated with ganglioside GM1 Deposited 2023-03-06	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.40 Å
8K8E Human gamma-secretase in complex with a substrate mimetic Deposited 2023-07-29	Different oligomeric state Different ligand/ion	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.60 Å
8KCO Cryo-EM structure of human gamma-secretase in complex with RO4929097 Deposited 2023-08-08	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 N60 2,2-dimethyl-N-[(7S)-6-oxo-5,7-dihydrobenzo[d][1]benzazepin-7-yl]-N'-(2,2,3,3,3-pentafluoropropyl)propanediamide × 1 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.80 Å
8KCP Cryo-EM structure of human gamma-secretase in complex with Crenigacestat Deposited 2023-08-08	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 N9C 4,4,4-tris(fluoranyl)-N-[(2S)-1-[[(7S)-5-(2-hydroxyethyl)-6-oxidanylidene-7H-pyrido[2,3-d][3]benzazepin-7-yl]amino]-1-oxidanylidene-propan-2-yl]butanamide × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.00 Å
8KCS Cryo-EM structure of human gamma-secretase in complex with BMS906024 Deposited 2023-08-08	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 Q70 Osugacestat × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.40 Å
8KCU Cryo-EM structure of human gamma-secretase in complex with MK-0752 Deposited 2023-08-08	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain B 1–467（467 aa）	Not recorded	PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 OL9 MK-0752 × 1 NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.70 Å
8OQY Structure of apo form of human gamma-secretase PSEN1 APH-1B isoform reconstituted into lipid nanodisc Deposited 2023-04-12	Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 7 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.30 Å
8OQZ Structure of human gamma-secretase PSEN1 APH-1B isoform reconstituted into lipid nanodisc in complex with Ab46 Deposited 2023-04-12	Different mutation/modification Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain B 1–467（467 aa）	Mutation：D257A	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 8 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 14	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.40 Å
8X52 Cryo-EM structure of human gamma-secretase in complex with Abeta49 Deposited 2023-11-16	Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 CLR CHOLESTEROL × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å
8X53 Cryo-EM structure of human gamma-secretase in complex with Abeta46 Deposited 2023-11-16	Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 3 CLR CHOLESTEROL × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.00 Å
8X54 Cryo-EM structure of human gamma-secretase in complex with APP-C99 Deposited 2023-11-16	Different oligomeric state Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 5 PDB declaration: pentameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 3 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å
9K95 Cryo-EM structure of human gamma-secretase in complex with compound E Deposited 2024-10-25	Different ligand/ion Different structure-quality metrics	Assembly 1 Other combination Heteromer；Protein × 4 PDB declaration: tetrameric	Chain B 1–467（467 aa）	Not recorded	NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 6 PC1 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE × 2 A1D6X (2~{S})-2-[2-[3,5-bis(fluoranyl)phenyl]ethanoylamino]-~{N}-[(3~{S})-1-methyl-2-oxidanylidene-5-phenyl-3~{H}-1,4-benzodiazepin-3-yl]propanamide × 1 CLR CHOLESTEROL × 3	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å

25 other PDB entries and 25 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence

UniProt name	PSN1_HUMAN
Isoform	—
PDB entities	4
Chains and sequence ranges	Author chain B； PDBConstruct 1–467； UniProt 1–467

The page prioritizes protein identity, the current assembly, associated components, oligomeric state and cross-PDB links. Chain mapping and sequence ranges are retained as data evidence. Internal IDs, import timestamps and assembly operation expressions are maintenance fields and are not shown here.

SAXS scattering curve SAXS Profile

P(r) Distance Distribution P(r) Distribution

Download Download SAXS (.dat) P(r) (.pr.out) CIF

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2. Structure Basics 2. Structure Basics

Entry ID entry_id	8kct
Deposition date deposition_date	2023-08-08
Structure title title	Cryo-EM structure of human gamma-secretase in complex with Nirogacestat
Keywords keywords	Intramembrane protease, gamma-secretase, gamma-secretase inhibitor, MEMBRANE PROTEIN, MEMBRANE PROTEIN-HYDROLASE complex; MEMBRANE PROTEIN
Experimental Method method	ELECTRON MICROSCOPY

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3. SAXS Parameters (CRYSOL theoretical calculation) 3. SAXS Parameters (CRYSOL)

Radius of gyration Rg (Guinier) rg_guinier	39.96 Å
Radius of gyration Rg (electron density) rg_electron	39.63 Å
Forward intensity I(0) i0	300914000.00
Molecular weight molecular_weight	153420.0 kDa
Excluded volume excluded_volume	196910 Å³
Envelope volume envelope_volume	265280 Å³
Hydration-shell volume shell_volume	55774 Å³
Envelope diameter envelope_diameter	139.8 Å
Shell Rg shell_rg	45.42 Å
Envelope Rg envelope_rg	38.88 Å
Shape Rg shape_rg	39.60 Å
Total Rg total_rg	40.09 Å
Total atoms total_atoms	10839
Residues n_residues	1313
Spherical-harmonic order n_harmonics	20
q range q_range	— – 0.5000 Å⁻¹
Data points n_points	101
Shell type shell_type	directional
Solvent electron density solvent_density	0.3340 e/Å³
Shell contrast contrast_shell	0.0300 e/Å³
CRYSOL version crysol_version	4.1.3

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4. P(r) Distance Distribution (GNOM inversion) 4. P(r) Analysis (GNOM)

Maximum dimension Dmax dmax	135.4 Å
Rg (real space) rg_real	40.03 Å
Rg uncertainty (real space) rg_real_error	1.06 Å
I(0) (real space) i0_real	3.0090e+08
I(0) uncertainty (real space) i0_real_error	5.0870e+06
Rg (reciprocal space) rg_reciprocal	39.99 Å
I(0) (reciprocal space) i0_reciprocal	300900000.0000
Solution quality estimate total_estimate	0.8841
Solution quality rating solution_quality	GOOD a GOOD solution
P(r) peaks n_peaks	2
Primary peak position r_peak_primary	44.0 Å
Skewness Skewness skewness	0.349
Kurtosis Kurtosis kurtosis	-0.440
Angular range angular_range	— – 0.2000 Å⁻¹
Current regularization parameter α current_alpha	0.0000
Highest regularization parameter α highest_alpha	38290000.0000
Real-space data points n_real_points	41
GNOM version gnom_version	4.1.3
Quality Criteria quality_criteria	AN1: 0.000; Oscil: 0.873; Stabil: 1.000; Sysdev: 1.000; Positv: 1.000; Valcen: 0.971; Smooth: 0.898

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5. Crystallography and Experiment 5. Crystallography & Experiment

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6. Entities and Polymers Entities & Polymers (10)

Entity 1 Entity 1 polymer

Description description	Nicastrin
Molecular weight formula_weight	77622.6 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	A
Atom count atom_count	10839

MATAGGGSGADPGSRGLLRLLSFCVLLAGLCRGNSVERKIYIPLNKTAPCVRLLNATHQIGCQSSISGDTGVIHVVEKEEDLQWVLTDGPNPPYMVLLESKHFTRDLMEKLKGRTSRIAGLAVSLTKPSPASGFSPSVQCPNDGFGVYSNSYGPEFAHCREIQWNSLGNGLAYEDFSFPIFLLEDENETKVIKQCYQDHNLSQNGSAPTFPLCAMQLFSHMHAVISTATCMRRSSIQSTFSINPEIVCDPLSDYNVWSMLKPINTTGTLKPDDRVVVAATRLDSRSFFWNVAPGAESAVASFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKFPVQLENVDSFVELGQVALRTSLELWMHTDPVSQKNESVRNQVEDLLATLEKSGAGVPAVILRRPNQSQPLPPSSLQRFLRARNISGVVLADHSGAFHNKYYQSIYDTAENINVSYPEWLSPEEDLNFVTDTAKALADVATVLGRALYELAGGTNFSDTVQADPQTVTRLLYGFLIKANNSWFQSILRQDLRSYLGDGPLQHYIAVSSPTNTTYVVQYALANLTGTVVNLTREQCQDPSKVPSENKDLYEYSWVQGPLHSNETDRLPRCVRSTARLARALSPAFELSQWSSTEYSTWTESRWKDIRARIFLIASKELELITLTVGFGILIFSLIVTYCINAKADVLFIAP

来源 Source

来源生物 organism	Homo sapiens
通用名 common_name	human
NCBI Class编号 ncbi_taxonomy_id	9606
宿主生物 host_organism	Homo sapiens

Entity 2 Entity 2 polymer

Description description	Gamma-secretase subunit APH-1A
Molecular weight formula_weight	29017.9 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	C

MGAAVFFGCTFVAFGPAFALFLITVAGDPLRVIILVAGAFFWLVSLLLASVVWFILVHVTDRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYVSGLSFGIISGVFSVINILADALGPGVVGIHGDSPYYFLTSAFLTAAIILLHTFWGVVFFDACERRRYWALGLVVGSHLLTSGLTFLNPWYEASLLPIYAVTVSMGLWAFITAGGSLRSIQRSLLCRRQEDSRVMVYSALRIPPED

来源 Source

来源生物 organism	Homo sapiens
通用名 common_name	human
NCBI Class编号 ncbi_taxonomy_id	9606
宿主生物 host_organism	Homo sapiens

Entity 3 Entity 3 polymer

Description description	Gamma-secretase subunit PEN-2
Molecular weight formula_weight	12038.0 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	D

MNLERVSNEEKLNLCRKYYLGGFAFLPFLWLVNIFWFFREAFLVPAYTEQSQIKGYVWRSAVGFLFWVIVLTSWITIFQIYRPRWGALGDYLSFTIPLGTP

来源 Source

来源生物 organism	Homo sapiens
通用名 common_name	human
NCBI Class编号 ncbi_taxonomy_id	9606
宿主生物 host_organism	Homo sapiens

Entity 4 Entity 4 polymer

Description description	Presenilin-1
Molecular weight formula_weight	52713.5 kDa
EC 编号 ec_number	3.4.23.-
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	B

MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSRQVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTEDTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFIYLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKYLPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAEGDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAAVQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCLTLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI

来源 Source

来源生物 organism	Homo sapiens
通用名 common_name	human
NCBI Class编号 ncbi_taxonomy_id	9606
宿主生物 host_organism	Homo sapiens

Entity 5 Entity 5 branched

Description description	2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
Molecular weight formula_weight	424.4 kDa
Source method src_method	man
Copy count entity_count	5

Entity 6 Entity 6 branched

Description description	;beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose ;
Molecular weight formula_weight	910.8 kDa
Source method src_method	man
Copy count entity_count	1

Entity 7 Entity 7 non-polymer

Description description	2-acetamido-2-deoxy-beta-D-glucopyranose
Molecular weight formula_weight	221.2 kDa
Source method src_method	syn
Copy count entity_count	6

Entity 8 Entity 8 non-polymer

Description description	CHOLESTEROL
Molecular weight formula_weight	386.7 kDa
Source method src_method	syn
Copy count entity_count	3

Entity 9 Entity 9 non-polymer

Description description	1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE
Molecular weight formula_weight	790.1 kDa
Source method src_method	syn
Copy count entity_count	2

Entity 10 Entity 10 non-polymer

Description description	Nirogacestat
Molecular weight formula_weight	489.6 kDa
Source method src_method	syn
Copy count entity_count	1

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8. Citations (1)

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Unit-cell length a length_a	1.000 Å
Unit-cell length b length_b	1.000 Å
Unit-cell length c length_c	1.000 Å
Unit-cell angle α angle_alpha	90.00 °
Unit-cell angle β angle_beta	90.00 °
Unit-cell angle γ angle_gamma	90.00 °
Molecules per unit cell Z z_pdb	—

Space group space_group	P 1
Space-group number int_tables_number	1
Crystal system crystal_system	—

Resolution resolution	2.60 Å
Resolution测定方法 resolution_method	—
颗粒数 num_particles	1047939

fit	/app/data/saxs_computation/kc/8kct/8kct.fit
pddf	/app/data/pr_computation/kc/8kct/8kct.pr.out
profile	/app/data/saxs_computation/kc/8kct/8kct.dat

Cryo-EM structure of human gamma-secretase in complex with Nirogacestat

1. Protein Identity and Related Structures Protein Identity & Related Structures

Nicastrin

State in the Current Structure

Other States of the Same Protein in the Database

Gamma-secretase subunit APH-1A

State in the Current Structure

Other States of the Same Protein in the Database

Gamma-secretase subunit PEN-2

State in the Current Structure

Other States of the Same Protein in the Database

Presenilin-1

State in the Current Structure

Other States of the Same Protein in the Database

SAXS scattering curve SAXS Profile

P(r) Distance Distribution P(r) Distribution

2. Structure Basics 2. Structure Basics

3. SAXS Parameters (CRYSOL theoretical calculation) 3. SAXS Parameters (CRYSOL)

4. P(r) Distance Distribution (GNOM inversion) 4. P(r) Analysis (GNOM)

5. Crystallography and Experiment 5. Crystallography & Experiment

Unit cell Unit Cell

Symmetry Symmetry

冷冻电镜 EM 3D

6. Entities and Polymers Entities & Polymers (10)

Entity 1 Entity 1 polymer

Polymer Polymer

来源 Source

Entity 2 Entity 2 polymer

Polymer Polymer

来源 Source

Entity 3 Entity 3 polymer

Polymer Polymer

来源 Source

Entity 4 Entity 4 polymer

Polymer Polymer

来源 Source

Entity 5 Entity 5 branched

Entity 6 Entity 6 branched

Entity 7 Entity 7 non-polymer

Entity 8 Entity 8 non-polymer

Entity 9 Entity 9 non-polymer

Entity 10 Entity 10 non-polymer

8. Citations (1)

9. Files and Curves (10)

Files (7)

Curves (3)