9c76

LRRK2 Roc domain RP (Ras-pocket) complexed to Divarasib

Method: X-RAY DIFFRACTION D_max: 78.6 Å Quality: GOOD

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

Leucine-rich repeat serine/threonine-protein kinase 2

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	Protein homooligomer Homooligomer Protein × 2 PDB declaration: dimeric（2） Consistent with protein copy count	Chain A； UniProt 1329–1516 Chain B； UniProt 1329–1516	Fragment：Roc domain Mutation：N1342A, T1343C, P1433H, W1434Y, N1437Q, K1460A, K1463A, C1465A (Uniprot numbering)	GDP GUANOSINE-5'-DIPHOSPHATE × 2 BR BROMIDE ION × 3 MG MAGNESIUM ION × 2 F FLUORIDE ION × 1 A1AWR 1-{(3S)-4-[(7M)-7-[6-amino-4-methyl-3-(trifluoromethyl)pyridin-2-yl]-6-chloro-8-fluoro-2-{[(2S)-1-methylpyrrolidin-2-yl]methoxy}quinazolin-4-yl]-3-methylpiperazin-1-yl}propan-1-one × 2 IOD IODIDE ION × 1	X-RAY DIFFRACTION X-ray crystallization conditions：VAPOR DIFFUSION, SITTING DROP；pH 6.5；277 K；Morpheus Fusion C7: 30 mM Halides 0.12 M Monosaccharide 1 0.1 M Buffer System 1 pH 6.5 30% Precipitant mix 1	Resolution 2.30 Å R-free 0.267

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 9C76	Assembly / Oligomeric State	Construct	Mutations and Modifications	Ligands, Ions and Non-polymers	Method and Experimental Conditions	Structure Quality
3D6T Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase Deposited 2008-05-20	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain B 1336–1505（170 aa） Fragment：Miro domain	Non-standard monomer：Yes (specific site not provided by mmCIF)	MG MAGNESIUM ION × 1 GDP GUANOSINE-5'-DIPHOSPHATE × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8；298 K；30% PEG 4000, 100mM MgCl2, 0.1M Tris, 5mM GTP, pH 8.0, VAPOR DIFFUSION, SITTING DROP, temperature 298K	Resolution 2.43 Å R-free 0.307
3D6T Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase Deposited 2008-05-20	Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 2 Protein homooligomer Homooligomer；Protein × 2 PDB declaration: dimeric	Chain B 1336–1505（170 aa） Fragment：Miro domain	Non-standard monomer：Yes (specific site not provided by mmCIF)	MG MAGNESIUM ION × 2 GDP GUANOSINE-5'-DIPHOSPHATE × 2	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8；298 K；30% PEG 4000, 100mM MgCl2, 0.1M Tris, 5mM GTP, pH 8.0, VAPOR DIFFUSION, SITTING DROP, temperature 298K	Resolution 2.43 Å R-free 0.307
5MY9 Crystal structure of human 14-3-3 sigma in complex with LRRK2 peptide pS935 Deposited 2017-01-26	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric	Chain P 929–941（13 aa） Fragment：UNP Residues 929-941	Non-standard monomer：Yes (specific site not provided by mmCIF)	CA CALCIUM ION × 6 CL CHLORIDE ION × 2	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 7.4；277 K；HEPES, NaCl, DTT	Resolution 1.33 Å R-free 0.201
5MYC Crystal structure of human 14-3-3 sigma in complex with LRRK2 peptide pS910 Deposited 2017-01-26	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric	Chain P 904–941（38 aa）	Non-standard monomer：Yes (specific site not provided by mmCIF)	CA CALCIUM ION × 4 CL CHLORIDE ION × 2 NA SODIUM ION × 2	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 7.3；277 K；HEPES, NaCl2, PEG400, Glycerol	Resolution 1.46 Å R-free 0.189
6DLO Crystal structure of LRRK2 WD40 domain dimer Deposited 2018-06-02	Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein homooligomer Homooligomer；Protein × 2 PDB declaration: dimeric	Chain A 2142–2527（386 aa） Fragment：WD40 domain residues 2142-2527 Chain B 2142–2527（386 aa） Fragment：WD40 domain residues 2142-2527	Not recorded	No recorded non-water small molecule	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；289 K；0.1 M Tris-HCl at pH 8.5, 1 M LiCl, 16% polyethylene glycol (PEG) 6000, and 10% additive of 30% galactose	Resolution 2.70 Å R-free 0.275
6DLP Crystal structure of LRRK2 WD40 domain dimer Deposited 2018-06-02	Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein homooligomer Homooligomer；Protein × 2 PDB declaration: dimeric	Chain A 2142–2527（386 aa） Fragment：WD40 domain residues 2142-2527 Chain B 2142–2527（386 aa） Fragment：WD40 domain residues 2142-2527	Not recorded	PT PLATINUM (II) ION × 6	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；289 K；0.1 M Tris-HCl at pH 8.5, 1 M LiCl, 16% polyethylene glycol (PEG) 6000, and 10% additive of 30% galactose. The crystal was soaked in 1 mM trans-platinum (II) diammine dichloride for 1.5 hours	Resolution 4.00 Å R-free 0.263
6OJE Dimeric structure of LRRK2 GTPase domain Deposited 2019-04-11	Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein homooligomer Homooligomer；Protein × 2 PDB declaration: dimeric	Chain A 1329–1520（192 aa） Fragment：GTPase domain of leucine-rich repeat kinase 2 Chain B 1329–1520（192 aa） Fragment：GTPase domain of leucine-rich repeat kinase 2	Not recorded	MG MAGNESIUM ION × 4 GDP GUANOSINE-5'-DIPHOSPHATE × 2	X-RAY DIFFRACTION X-ray crystallization conditions MICROBATCH；pH 6.5；298 K；100mM KSCN, 25% PEGMME 2000, 0.1M BisTris pH 6.5	Resolution 1.95 Å R-free 0.196
6OJF Dimeric structure of LRRK2 GTPase domain Deposited 2019-04-11	Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein homooligomer Homooligomer；Protein × 2 PDB declaration: dimeric	Chain A 1329–1520（192 aa） Fragment：GTPase domain of leucine-rich repeat kinase 2 Chain B 1329–1520（192 aa） Fragment：GTPase domain of leucine-rich repeat kinase 2	Mutation：K1460A, K1463A Mutation：K1460A, K1463A	MG MAGNESIUM ION × 4 GDP GUANOSINE-5'-DIPHOSPHATE × 2	X-RAY DIFFRACTION X-ray crystallization conditions MICROBATCH；pH 6.5；298 K；100mM KSCN, 25% PEGMME 2000, 0.1M BisTris pH 6.5	Resolution 1.60 Å R-free 0.158
6VNO Cryo-EM structure of the C-terminal half of the Parkinson's Disease-linked protein Leucine Rich Repeat Kinase 2 (LRRK2) Deposited 2020-01-29	Different construct Different mutation/modification 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 1327–2527（1201 aa）	Non-standard monomer：Yes (specific site not provided by mmCIF)	GDP GUANOSINE-5'-DIPHOSPHATE × 1 MG MAGNESIUM ION × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.50 Å
6VP6 Cryo-EM structure of the C-terminal half of the Parkinson's Disease-linked protein Leucine Rich Repeat Kinase 2 (LRRK2) Deposited 2020-02-01	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein homooligomer Homooligomer；Protein × 3 PDB declaration: trimeric	Chain A 1327–2527（1201 aa） Chain B 1327–2527（1201 aa） Chain C 1327–2527（1201 aa）	Non-standard monomer：Yes (specific site not provided by mmCIF) Non-standard monomer：Yes (specific site not provided by mmCIF) Non-standard monomer：Yes (specific site not provided by mmCIF)	GDP GUANOSINE-5'-DIPHOSPHATE × 1 MG MAGNESIUM ION × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.47 Å
6VP7 Cryo-EM structure of the C-terminal half of the Parkinson's Disease-linked protein Leucine Rich Repeat Kinase 2 (LRRK2) Deposited 2020-02-01	Different construct Different mutation/modification 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 1327–2527（1201 aa）	Non-standard monomer：Yes (specific site not provided by mmCIF)	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.50 Å
6VP8 Cryo-EM structure of the C-terminal half of the Parkinson's Disease-linked protein Leucine Rich Repeat Kinase 2 (LRRK2) Deposited 2020-02-01	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein homooligomer Homooligomer；Protein × 3 PDB declaration: trimeric	Chain A 1330–2527（1198 aa） Chain B 1670–1950（281 aa） Chain C 2140–2498（359 aa）	Non-standard monomer：Yes (specific site not provided by mmCIF)	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.50 Å
6XAF 1.9A crystal structure of the GTPase domain of Parkinson's disease-associated protein LRRK2 carrying R1398H Deposited 2020-06-04	Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein homooligomer Homooligomer；Protein × 2 PDB declaration: dimeric	Chain A 1329–1520（192 aa） Fragment：GTPase domain (UNP residues 1329-1520) Chain B 1329–1520（192 aa） Fragment：GTPase domain (UNP residues 1329-1520)	Mutation：R1398H, K1460A, K1463A Mutation：R1398H, K1460A, K1463A	MG MAGNESIUM ION × 2 GDP GUANOSINE-5'-DIPHOSPHATE × 2	X-RAY DIFFRACTION X-ray crystallization conditions MICROBATCH；pH 6.5；298 K；100 mM potassium thiocyanate, 25% PEG2000 MME, 0.1 M Bis-Tris, pH 6.5	Resolution 1.97 Å R-free 0.221
6XR4 Integrative in situ structure of Parkinsons disease-linked human LRRK2 Deposited 2020-07-10	Different construct Different mutation/modification Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein homooligomer Homooligomer；Protein × 2 PDB declaration: dimeric	Chain A 1–2527（2527 aa） Chain B 1–2527（2527 aa）	Mutation：I2020T Mutation：I2020T	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer pH 7 cryo-EM vitrification conditions Cryogen ETHANE-PROPANE	Resolution 14.00 Å
7LHT Structure of the LRRK2 dimer Deposited 2021-01-26	Different construct Different mutation/modification Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein homooligomer Homooligomer；Protein × 2 PDB declaration: dimeric	Chain A 1–2527（2527 aa） Chain B 1–2527（2527 aa）	Not recorded	GDP GUANOSINE-5'-DIPHOSPHATE × 2 ATP ADENOSINE-5'-TRIPHOSPHATE × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 8 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.50 Å
7LHW Structure of the LRRK2 monomer Deposited 2021-01-26	Different construct Different mutation/modification 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 1–2527（2527 aa）	Not recorded	GDP GUANOSINE-5'-DIPHOSPHATE × 1 ATP ADENOSINE-5'-TRIPHOSPHATE × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 8 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.70 Å
7LI3 Structure of the LRRK2 G2019S mutant Deposited 2021-01-26	Different construct Different mutation/modification 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 1–2527（2527 aa）	Mutation：G2019S variant	GDP GUANOSINE-5'-DIPHOSPHATE × 1 ATP ADENOSINE-5'-TRIPHOSPHATE × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 8 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.80 Å
7LI4 Structure of LRRK2 after symmetry expansion Deposited 2021-01-26	Different construct Different mutation/modification 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 1–2527（2527 aa）	Not recorded	GDP GUANOSINE-5'-DIPHOSPHATE × 1 ATP ADENOSINE-5'-TRIPHOSPHATE × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 8 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.10 Å
7THY Structure of Leucine Rich Repeat Kinase 2's ROC domain interacting with the microtubule facing the minus end Deposited 2022-01-12	Different construct Different mutation/modification 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 1332–1525（194 aa） Fragment：ROC domain	Not recorded	GDP GUANOSINE-5'-DIPHOSPHATE × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4；This is the final dilution buffer. The incubation buffer consisted of 1x BRB80, 10% glycerol, 1mM DTT, 1mM GTP, 1mM MgCl2, 10 uM taxol, and 5 uM MLi-2. Sample was diluted 3-fold right before freezing with the final buffer. cryo-EM vitrification conditions Cryogen ETHANE	Resolution 5.20 Å
7THZ Structure of Leucine Rich Repeat Kinase 2's ROC domain interacting with the microtubule facing the plus end Deposited 2022-01-12	Different construct Different mutation/modification 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 1332–1525（194 aa） Fragment：ROC domain	Not recorded	GDP GUANOSINE-5'-DIPHOSPHATE × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4；This is the final dilution buffer. The incubation buffer consisted of 1x BRB80, 10% glycerol, 1mM DTT, 1mM GTP, 1mM MgCl2, 10 uM taxol, and 5 uM MLi-2. Sample was diluted 3-fold right before freezing with the final buffer. cryo-EM vitrification conditions Cryogen ETHANE	Resolution 5.00 Å
8FO2 Cryo-EM structure of Rab29-LRRK2 complex in the LRRK2 monomer state Deposited 2022-12-29	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain E 1–2527（2527 aa）	Not recorded	MG MAGNESIUM ION × 1 GNP PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER × 1 GDP GUANOSINE-5'-DIPHOSPHATE × 1 ATP ADENOSINE-5'-TRIPHOSPHATE × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 8 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 4.13 Å
8FO7 Cryo-EM structure of LRRK2 bound to type I inhibitor LRRK2-IN-1 Deposited 2022-12-29	Different construct Different mutation/modification 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 C 1327–2527（1201 aa）	Not recorded	GDP GUANOSINE-5'-DIPHOSPHATE × 1 4K4 2-[(2-methoxy-4-{[4-(4-methylpiperazin-1-yl)piperidin-1-yl]carbonyl}phenyl)amino]-5,11-dimethyl-5,11-dihydro-6H-pyrimido[4,5-b][1,4]benzodiazepin-6-one × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 7.5 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.52 Å
8FO8 Cryo-EM structure of Rab29-LRRK2 complex in the LRRK2 dimer state Deposited 2022-12-29	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric	Chain C 1–2527（2527 aa） Chain E 1–2527（2527 aa）	Not recorded	GDP GUANOSINE-5'-DIPHOSPHATE × 2 ATP ADENOSINE-5'-TRIPHOSPHATE × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 8 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.88 Å
8FO9 Cryo-EM structure of Rab29-LRRK2 complex in the LRRK2 tetramer state Deposited 2022-12-30	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 6 PDB declaration: hexameric	Chain A 1–2527（2527 aa） Chain C 1–2527（2527 aa） Chain E 1–2527（2527 aa） Chain F 1–2527（2527 aa）	Not recorded	GDP GUANOSINE-5'-DIPHOSPHATE × 4 ATP ADENOSINE-5'-TRIPHOSPHATE × 4	ELECTRON MICROSCOPY cryo-EM buffer pH 8 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.48 Å
8TXZ Structure of C-terminal LRRK2 bound to MLi-2 Deposited 2023-08-24	Different construct Different mutation/modification 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 1334–2527（1194 aa）	Not recorded	A1N (2~{R},6~{S})-2,6-dimethyl-4-[6-[5-(1-methylcyclopropyl)oxy-1~{H}-indazol-3-yl]pyrimidin-4-yl]morpholine × 1 GDP GUANOSINE-5'-DIPHOSPHATE × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE；Blot force = 3 Blot time = 4 seconds wait time = 20 seconds	Resolution 3.05 Å
8TYQ Structure of the C-terminal half of LRRK2 bound to GZD-824 (G2019S mutant) Deposited 2023-08-25	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain A 1–2527（2527 aa）	Mutation：G2019S	T3X 4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-3-[(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]benzamide × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.99 Å
8TZB Structure of the C-terminal half of LRRK2 bound to GZD-824 (I2020T mutant) Deposited 2023-08-26	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain A 1–2527（2527 aa）	Mutation：I2020T	T3X 4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-3-[(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]benzamide × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.10 Å
8TZC Structure of C-terminal LRRK2 bound to MLi-2 (G2019S mutant) Deposited 2023-08-26	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain A 1333–2527（1195 aa）	Not recorded	A1N (2~{R},6~{S})-2,6-dimethyl-4-[6-[5-(1-methylcyclopropyl)oxy-1~{H}-indazol-3-yl]pyrimidin-4-yl]morpholine × 1 GDP GUANOSINE-5'-DIPHOSPHATE × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE；Blot force = 3 Blot time = 4 seconds Wait time = 20 seconds	Resolution 2.70 Å
8TZE Structure of C-terminal half of LRRK2 bound to GZD-824 Deposited 2023-08-26	Different construct Different mutation/modification 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 1–2527（2527 aa）	Not recorded	T3X 4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-3-[(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]benzamide × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 2.90 Å
8TZF Structure of full length LRRK2 bound to GZD-824 (I2020T mutant) Deposited 2023-08-26	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain A 1–2527（2527 aa）	Mutation：I2020T	GDP GUANOSINE-5'-DIPHOSPHATE × 1 T3X 4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-3-[(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]benzamide × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.40 Å
8TZG Structure of C-terminal LRRK2 bound to MLi-2 (I2020T mutant) Deposited 2023-08-26	Different construct Different mutation/modification 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 1333–2522（1190 aa）	Not recorded	A1N (2~{R},6~{S})-2,6-dimethyl-4-[6-[5-(1-methylcyclopropyl)oxy-1~{H}-indazol-3-yl]pyrimidin-4-yl]morpholine × 1 GDP GUANOSINE-5'-DIPHOSPHATE × 1 MG MAGNESIUM ION × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE；Blot force = 3 Blot time = 4 seconds Wait time = 20 seconds	Resolution 2.70 Å
8TZH Structure of full-length LRRK2 bound to MLi-2 (I2020T mutant) Deposited 2023-08-26	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain A 1–2527（2527 aa）	Not recorded	A1N (2~{R},6~{S})-2,6-dimethyl-4-[6-[5-(1-methylcyclopropyl)oxy-1~{H}-indazol-3-yl]pyrimidin-4-yl]morpholine × 1 GDP GUANOSINE-5'-DIPHOSPHATE × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE；Blot force = 3 Blot time = 4 seconds Wait time = 20 seconds	Resolution 3.90 Å
8U1B C-terminal LRRK2 bound to E11 DARPin Deposited 2023-08-31	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain A 1334–2527（1194 aa）	Not recorded	No recorded non-water small molecule	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.70 Å
8U7L Cryo-EM structure of LRRK2 bound to type II inhibitor GZD824 Deposited 2023-09-15	Different construct Different mutation/modification Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein homooligomer Homooligomer；Protein × 2 PDB declaration: dimeric	Chain A 1–2527（2527 aa） Chain B 1–2527（2527 aa）	Not recorded	GDP GUANOSINE-5'-DIPHOSPHATE × 2 T3X 4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-3-[(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]benzamide × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 8 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.60 Å
8U8A Cryo-EM structure of LRRK2 bound to type II inhibitor ponatinib Deposited 2023-09-16	Different construct Different mutation/modification Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein homooligomer Homooligomer；Protein × 2 PDB declaration: dimeric	Chain B 1–2527（2527 aa） Chain C 1–2527（2527 aa）	Not recorded	0LI 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzam ide × 2 GDP GUANOSINE-5'-DIPHOSPHATE × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 8 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.40 Å
8U8B Cryo-EM structure of LRRK2 bound to type II inhibitor rebastinib Deposited 2023-09-16	Different construct Different mutation/modification Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein homooligomer Homooligomer；Protein × 2 PDB declaration: dimeric	Chain A 1–2527（2527 aa） Chain B 1–2527（2527 aa）	Not recorded	GDP GUANOSINE-5'-DIPHOSPHATE × 2 919 4-[4-({[3-tert-butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 8 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.70 Å
8VH4 Cryo-EM structure of Rab12-LRRK2 complex in the LRRK2 monomer state Deposited 2023-12-30	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain A 1–2527（2527 aa）	Not recorded	GDP GUANOSINE-5'-DIPHOSPHATE × 1 ANP PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER × 1 MG MAGNESIUM ION × 1 GNP PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 8 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 4.10 Å
8VH5 Cryo-EM structure of Rab12-LRRK2 complex in the LRRK2 dimer state Deposited 2023-12-30	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 1–2527（2527 aa） Chain C 1–2527（2527 aa）	Not recorded	GDP GUANOSINE-5'-DIPHOSPHATE × 2 ANP PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER × 2 MG MAGNESIUM ION × 2 GNP PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER × 2	ELECTRON MICROSCOPY cryo-EM buffer pH 8 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 4.00 Å
9CHO Autoinhibited full-length LRRK2(I2020T) on microtubules with MLi-2 Deposited 2024-07-01	Different construct Different mutation/modification 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 543–2527（1985 aa） Fragment：UNP residues 543-2527	Mutation：I2020T	GDP GUANOSINE-5'-DIPHOSPHATE × 1 A1N (2~{R},6~{S})-2,6-dimethyl-4-[6-[5-(1-methylcyclopropyl)oxy-1~{H}-indazol-3-yl]pyrimidin-4-yl]morpholine × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 7.80 Å
9CI3 Structure of the LRRK2/14-3-3 complex Deposited 2024-07-02	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 3 PDB declaration: trimeric	Chain A 1–2527（2527 aa）	Mutation：R50H variant Non-standard monomer：Yes (specific site not provided by mmCIF)	GDP GUANOSINE-5'-DIPHOSPHATE × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 8.3 cryo-EM vitrification conditions Cryogen ETHANE	Resolution 3.96 Å
9DMI Structure of the C-terminal half of LRRK2 bound to RN277 (Type-II inhibitor) Deposited 2024-09-13	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain A 1333–2527（1195 aa）	Not recorded	A1A7Q N-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-N'-{(3M)-3-[2-chloro-4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl}urea × 1	ELECTRON MICROSCOPY cryo-EM buffer pH 7.4 cryo-EM vitrification conditions Cryogen ETHANE；Blot time 4s Blot force 5 Waiting time 20s	Resolution 3.35 Å

40 other PDB entries and 41 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence

UniProt name	LRRK2_HUMAN
Isoform	—
PDB entities	1
Chains and sequence ranges	Author chain A； PDBConstruct 2–189； UniProt 1329–1516 Author chain B； PDBConstruct 2–189； UniProt 1329–1516

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	9c76
Deposition date deposition_date	2024-06-10
Structure title title	LRRK2 Roc domain RP (Ras-pocket) complexed to Divarasib
Keywords keywords	GTPase, Complex, chemical biology, switch II, SIGNALING PROTEIN; SIGNALING PROTEIN
Experimental Method method	X-RAY DIFFRACTION

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

Radius of gyration Rg (Guinier) rg_guinier	23.19 Å
Radius of gyration Rg (electron density) rg_electron	22.19 Å
Forward intensity I(0) i0	28928900.00
Molecular weight molecular_weight	40028.0 kDa
Excluded volume excluded_volume	49404 Å³
Envelope volume envelope_volume	58883 Å³
Hydration-shell volume shell_volume	22516 Å³
Envelope diameter envelope_diameter	81.3 Å
Shell Rg shell_rg	28.83 Å
Envelope Rg envelope_rg	22.66 Å
Shape Rg shape_rg	22.24 Å
Total Rg total_rg	22.87 Å
Total atoms total_atoms	5477
Residues n_residues	343
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	78.6 Å
Rg (real space) rg_real	23.21 Å
Rg uncertainty (real space) rg_real_error	0.46 Å
I(0) (real space) i0_real	2.8930e+07
I(0) uncertainty (real space) i0_real_error	3.8130e+05
Rg (reciprocal space) rg_reciprocal	23.20 Å
I(0) (reciprocal space) i0_reciprocal	28930000.0000
Solution quality estimate total_estimate	0.8761
Solution quality rating solution_quality	GOOD a GOOD solution
P(r) peaks n_peaks	2
Primary peak position r_peak_primary	25.4 Å
Skewness Skewness skewness	0.392
Kurtosis Kurtosis kurtosis	-0.317
Angular range angular_range	— – 0.3400 Å⁻¹
Current regularization parameter α current_alpha	0.0002
Highest regularization parameter α highest_alpha	5036000.0000
Real-space data points n_real_points	66
GNOM version gnom_version	4.1.3
Quality Criteria quality_criteria	AN1: 0.000; Oscil: 0.805; Stabil: 1.000; Sysdev: 1.000; Positv: 1.000; Valcen: 0.971; Smooth: 0.999

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5. Crystallography and Experiment 5. Crystallography & Experiment

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6. Entities and Polymers Entities & Polymers (8)

Entity 1 Entity 1 polymer

Description description	Leucine-rich repeat serine/threonine-protein kinase 2
Molecular weight formula_weight	21453.8 kDa
EC 编号 ec_number	2.7.11.1,3.6.5.-
Mutation mutation	N1342A, T1343C, P1433H, W1434Y, N1437Q, K1460A, K1463A, C1465A (Uniprot numbering)
Source method src_method	man
Copy count entity_count	2

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	A,B
Atom count atom_count	5573

SAVPYNRMKLMIVGACGSGKTTLLQQLMKTKKSDLGMQSATVGIDVKDWPIQIRDKRKRDLVLNVWDFAGREEFYSTHPHFMTQRALYLAVYDLSKGQAEVDAMKHYLFQIKARASSSPVILVGTHLDVSDEAQRAAAMSKITKELLNKRGFPAIRDYHFVNATEESDALAKLRKTIINESLNFKIRDQ

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	Escherichia coli

Entity 2 Entity 2 non-polymer

Description description	GUANOSINE-5'-DIPHOSPHATE
Molecular weight formula_weight	443.2 kDa
Source method src_method	syn
Copy count entity_count	2

Entity 3 Entity 3 non-polymer

Description description	BROMIDE ION
Molecular weight formula_weight	79.9 kDa
Source method src_method	syn
Copy count entity_count	3

Entity 4 Entity 4 non-polymer

Description description	MAGNESIUM ION
Molecular weight formula_weight	24.3 kDa
Source method src_method	syn
Copy count entity_count	2

Entity 5 Entity 5 non-polymer

Description description	FLUORIDE ION
Molecular weight formula_weight	19.0 kDa
Source method src_method	syn
Copy count entity_count	1

Entity 6 Entity 6 non-polymer

Description description	;1-{(3S)-4-[(7M)-7-[6-amino-4-methyl-3-(trifluoromethyl)pyridin-2-yl]-6-chloro-8-fluoro-2-{[(2S)-1-methylpyrrolidin-2-yl]methoxy}quinazolin-4-yl]-3-methylpiperazin-1-yl}propan-1-one ;
Molecular weight formula_weight	624.1 kDa
Source method src_method	syn
Copy count entity_count	2

Entity 7 Entity 7 non-polymer

Description description	IODIDE ION
Molecular weight formula_weight	126.9 kDa
Source method src_method	syn
Copy count entity_count	1

Entity 8 Entity 8 water

Description description	water
Molecular weight formula_weight	18.0 kDa
Source method src_method	nat
Copy count entity_count	96

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8. Citations (1)

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Unit-cell length a length_a	40.411 Å
Unit-cell length b length_b	98.379 Å
Unit-cell length c length_c	105.203 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	8

Space group space_group	P 21 21 21
Space-group number int_tables_number	19
Crystal system crystal_system	—

Resolution resolution	2.300 Å
Low-resolution limit resolution_low	35.220 Å
R factor r_factor	0.2310
R_work r_work	0.2268
R_free r_free	0.2668

fit	/app/data/saxs_computation/c7/9c76/9c76.fit
pddf	/app/data/pr_computation/c7/9c76/9c76.pr.out
profile	/app/data/saxs_computation/c7/9c76/9c76.dat