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8u7l

Cryo-EM structure of LRRK2 bound to type II inhibitor GZD824

Method: ELECTRON MICROSCOPY Dmax: 181.1 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

UniProt Q5S007

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 1–2527 Chain B； UniProt 1–2527 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

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 8U7L 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 method 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 method 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 method 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 method 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 ligand/ion Different experimental method 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 ligand/ion Different experimental method 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 ligand/ion Different experimental method 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 method 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 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 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 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 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 method 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 mutation/modification Different ligand/ion 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 ligand/ion 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 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 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 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 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 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 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 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 oligomeric state Different ligand/ion 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 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 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 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 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 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 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 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 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 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 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
8U8A Cryo-EM structure of LRRK2 bound to type II inhibitor ponatinib Deposited 2023-09-16 Different ligand/ion 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 ligand/ion 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 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 oligomeric state Different ligand/ion 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
9C76 LRRK2 Roc domain RP (Ras-pocket) complexed to Divarasib Deposited 2024-06-10 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 1329–1516（188 aa） Fragment：Roc domain
Chain B 1329–1516（188 aa） Fragment：Roc domain
Mutation：N1342A, T1343C, P1433H, W1434Y, N1437Q, K1460A, K1463A, C1465A (Uniprot numbering) 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
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 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 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 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 1–2527； UniProt 1–2527 Author chain B； PDBConstruct 1–2527； UniProt 1–2527

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

SAXS profile for 8u7l

P(r) Distance Distribution P(r) Distribution

P(r) distribution for 8u7l
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2. Structure Basics 2. Structure Basics

Entry ID entry_id8u7l
Deposition date deposition_date2023-09-15
最后修订 last_revision2024-01-31
Structure title titleCryo-EM structure of LRRK2 bound to type II inhibitor GZD824
Keywords keywords;Cryo-EM, Parkinson's disease, Kinase, LRRK2, type II inhibitor, HYDROLASE ;; HYDROLASE
Experimental Method methodELECTRON MICROSCOPY
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3. SAXS Parameters (CRYSOL theoretical calculation) 3. SAXS Parameters (CRYSOL)

Radius of gyration Rg (Guinier) rg_guinier57.96 Å
Radius of gyration Rg (electron density) rg_electron57.45 Å
Forward intensity I(0) i01579560000.00
Molecular weight molecular_weight343720.0 kDa
Excluded volume excluded_volume434150 ų
Envelope volume envelope_volume705110 ų
Hydration-shell volume shell_volume101190 ų
Envelope diameter envelope_diameter173.3 Å
Shell Rg shell_rg62.61 Å
Envelope Rg envelope_rg54.52 Å
Shape Rg shape_rg57.42 Å
Total Rg total_rg57.70 Å
Total atoms total_atoms24222
Residues n_residues3410
Spherical-harmonic order n_harmonics20
q range q_range— – 0.5000 Å−1
Data points n_points101
Shell type shell_typedirectional
Solvent electron density solvent_density0.3340 e/ų
Shell contrast contrast_shell0.0300 e/ų
CRYSOL version crysol_version4.1.3
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4. P(r) Distance Distribution (GNOM inversion) 4. P(r) Analysis (GNOM)

Maximum dimension Dmax dmax181.1 Å
Rg (real space) rg_real57.72 Å
Rg uncertainty (real space) rg_real_error1.67 Å
I(0) (real space) i0_real1.5800e+09
I(0) uncertainty (real space) i0_real_error3.2370e+07
Rg (reciprocal space) rg_reciprocal58.13 Å
I(0) (reciprocal space) i0_reciprocal1581000000.0000
Solution quality estimate total_estimate0.8783
Solution quality rating solution_quality GOOD a GOOD solution
P(r) peaks n_peaks1
Primary peak position r_peak_primary73.8 Å
Skewness Skewness skewness0.065
Kurtosis Kurtosis kurtosis-0.694
Angular range angular_range— – 0.1350 Å−1
Current regularization parameter α current_alpha0.0000
Highest regularization parameter α highest_alpha94790000.0000
Real-space data points n_real_points28
GNOM version gnom_version4.1.3
Quality Criteria quality_criteria AN1: 0.000; Oscil: 0.968; Stabil: 1.000; Sysdev: 1.000; Positv: 1.000; Valcen: 0.992; Smooth: 0.518
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5. Crystallography and Experiment 5. Crystallography & Experiment

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6. Entities and Polymers Entities & Polymers (3)

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8. Citations (1)

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9. Files and Curves (10)