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6i3u

Optimization of potent and selective ATM inhibitors suitable for a proof-of-concept study in Huntington's disease models

Method: X-RAY DIFFRACTION Dmax: 85.7 Å Quality: EXCELLENT
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1. Protein Identity and Related Structures Protein Identity & Related Structures

Phosphatidylinositol 3-kinase catalytic subunit type 3

Homo sapiens

UniProt Q8NEB9

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 monomer Monomer Protein × 1 PDB declaration: monomeric（1） Consistent with protein copy count Chain A； UniProt 268–879 Mutation：F612A, L616N, I634L, M682L, F684W, Q686_S687insG H2E 2-morpholin-4-yl-6-[7-[(2~{R})-1-morpholin-4-ylpropan-2-yl]oxy-9~{H}-thioxanthen-4-yl]pyran-4-one × 1 X-RAY DIFFRACTION X-ray crystallization conditions：VAPOR DIFFUSION, HANGING DROP；pH 7；293 K；1.4 M Sodium Malonate pH 7.0, 0.1 M Bis-Tris Propane pH 7.0 Resolution 2.09 Å R-free 0.236

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 6I3U Assembly / Oligomeric State Construct Mutations and Modifications Ligands, Ions and Non-polymers Method and Experimental Conditions Structure Quality
11MM The structure of human Vacuolar Protein Sorting 34 catalytic domain bound to RD-II-81 Deposited 2026-03-05 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 290–871（582 aa）
Not recorded GOL GLYCEROL × 2 A1C9V (8S)-3-[6-(propan-2-yl)-1,3-benzothiazol-2-yl]pyrazolo[1,5-a]pyrimidine × 1 DMS DIMETHYL SULFOXIDE × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION；pH 6；298 K；BIS-TRIS pH 6.5, 20% w/v Polyethylene glycol monomethyl ether 5,000
Resolution 2.69 Å R-free 0.265
11YC The structure of human Vacuolar Protein Sorting 34 catalytic domain bound to RD-II-123 Deposited 2026-03-17 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 290–871（582 aa）
Not recorded A1DAY (8S)-3-(6-butyl-1,3-benzothiazol-2-yl)pyrazolo[1,5-a]pyrimidine × 1 EDO 1,2-ETHANEDIOL × 1 PEG DI(HYDROXYETHYL)ETHER × 1 CL CHLORIDE ION × 4 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION；pH 6；298 K；Ammonium Acetate, HEPES, Polyethylene glycol 3,350
Resolution 2.41 Å R-free 0.220
13BV Cryo-EM structure of human PI3KC3-C1 complex Deposited 2026-04-28 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 B 1–887（887 aa）
Not recorded MYR MYRISTIC ACID × 1 GDP GUANOSINE-5'-DIPHOSPHATE × 1 MG MAGNESIUM ION × 1 ELECTRON MICROSCOPY
cryo-EM buffer pH 7.5
cryo-EM vitrification conditions Cryogen ETHANE
Resolution 3.77 Å
3IHY Human PIK3C3 crystal structure Deposited 2009-07-31 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 282–879（598 aa） Fragment：UNP residues 282-879
Not recorded No recorded non-water small molecule X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8.5；277 K；0.2M ammonium acetate 25% PEG3350 0.1M Tris, pH 8.5, VAPOR DIFFUSION, SITTING DROP, temperature 277K
Resolution 2.80 Å R-free 0.255
3IHY Human PIK3C3 crystal structure Deposited 2009-07-31 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 282–879（598 aa） Fragment：UNP residues 282-879
Not recorded No recorded non-water small molecule X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8.5；277 K；0.2M ammonium acetate 25% PEG3350 0.1M Tris, pH 8.5, VAPOR DIFFUSION, SITTING DROP, temperature 277K
Resolution 2.80 Å R-free 0.255
3IHY Human PIK3C3 crystal structure Deposited 2009-07-31 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 3 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain C 282–879（598 aa） Fragment：UNP residues 282-879
Not recorded No recorded non-water small molecule X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8.5；277 K；0.2M ammonium acetate 25% PEG3350 0.1M Tris, pH 8.5, VAPOR DIFFUSION, SITTING DROP, temperature 277K
Resolution 2.80 Å R-free 0.255
3IHY Human PIK3C3 crystal structure Deposited 2009-07-31 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 4 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain D 282–879（598 aa） Fragment：UNP residues 282-879
Not recorded No recorded non-water small molecule X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8.5；277 K；0.2M ammonium acetate 25% PEG3350 0.1M Tris, pH 8.5, VAPOR DIFFUSION, SITTING DROP, temperature 277K
Resolution 2.80 Å R-free 0.255
3IHY Human PIK3C3 crystal structure Deposited 2009-07-31 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 5 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain E 282–879（598 aa） Fragment：UNP residues 282-879
Not recorded No recorded non-water small molecule X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8.5；277 K；0.2M ammonium acetate 25% PEG3350 0.1M Tris, pH 8.5, VAPOR DIFFUSION, SITTING DROP, temperature 277K
Resolution 2.80 Å R-free 0.255
3LS8 Crystal structure of human PIK3C3 in complex with 3-[4-(4-Morpholinyl)thieno[3,2-d]pyrimidin-2-yl]-phenol Deposited 2010-02-12 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 268–879（612 aa） Fragment：UNP Residues 268-879
Not recorded AJZ 3-(4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-yl)phenol × 1 CL CHLORIDE ION × 2 GOL GLYCEROL × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 7.5；293 K；25% PEG3350, 0.2M ammonium acetate, 0.1M hepes pH 7.5, VAPOR DIFFUSION, SITTING DROP, temperature 293K
Resolution 2.25 Å R-free 0.251
3LS8 Crystal structure of human PIK3C3 in complex with 3-[4-(4-Morpholinyl)thieno[3,2-d]pyrimidin-2-yl]-phenol Deposited 2010-02-12 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 268–879（612 aa） Fragment：UNP Residues 268-879
Not recorded AJZ 3-(4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-yl)phenol × 1 CL CHLORIDE ION × 2 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 7.5；293 K；25% PEG3350, 0.2M ammonium acetate, 0.1M hepes pH 7.5, VAPOR DIFFUSION, SITTING DROP, temperature 293K
Resolution 2.25 Å R-free 0.251
4OYS CRYSTAL STRUCTURE OF VPS34 IN COMPLEX WITH SAR405. Deposited 2014-02-13 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 282–879（598 aa） Fragment：UNP residues 282-879
Not recorded SO4 SULFATE ION × 4 1TT (8S)-9-[(5-chloranylpyridin-3-yl)methyl]-2-[(3R)-3-methylmorpholin-4-yl]-8-(trifluoromethyl)-6,7,8,9a-tetrahydro-3H-pyrimido[1,2-a]pyrimidin-4-one × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 7.5；293 K；1.9 M ammonium sulfate, 100 mM Tris pH 8.5
Resolution 2.90 Å R-free 0.248
4PH4 The crystal structure of Human VPS34 in complex with PIK-III Deposited 2014-05-04 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 293–887（595 aa） Fragment：UNP residues 293-887
Not recorded GOL GLYCEROL × 1 2UG 4'-(cyclopropylmethyl)-N~2~-(pyridin-4-yl)-4,5'-bipyrimidine-2,2'-diamine × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；303.15 K；VPS34 protein and PIK-III were mixed and incubated on ice for 1 hr (final PIK-III concentration was 1 mM). Prior to crystallization, the mixture was passed through a 0.2 um filter. The protein:ligand complex was crystallized using the hanging drop vapor diffusion method in Nextal plates: 6 uL of protein solution was mixed with 4 uL of precipitant, which consisted of 20% (w/v) PEG 3350, 100 mM bis-tris propane, and 200 mM Na-K-phosphate. The resulting drop was suspended over a reservoir of 0.3 mL of precipitant and sealed with a screw cap. The crystals grew at 30 degC in approximately 12-24 hr.
Resolution 2.80 Å R-free 0.223
4UWF Discovery of (2S)-8-((3R)-3-Methylmorpholin-4-yl)-1-(3-methyl-2-oxo- butyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido(1,2-a)pyrimidin-6- one: a Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors Deposited 2014-08-12 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 282–879（598 aa） Fragment：VPS34 HELICAL AND KINASE DOMAINS, RESIDUES 282-879
Not recorded EUT (8S)-9-[3,5-bis(fluoranyl)phenyl]-2-morpholin-4-yl-8-(trifluoromethyl)-7,8-dihydro-6H-pyrimido[1,2-a]pyrimidin-4-one × 1 X-RAY DIFFRACTION
X-ray crystallization conditions pH 8；292 K；NA-MALONATE 1.4M, TRIS 100MM PH 8 AT 19C
Resolution 2.99 Å R-free 0.246
4UWG Discovery of (2S)-8-((3R)-3-Methylmorpholin-4-yl)-1-(3-methyl-2-oxo- butyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido(1,2-a)pyrimidin-6- one: a Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors Deposited 2014-08-12 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 282–879（598 aa） Fragment：VPS34 HELICAL AND KINASE DOMAINS, RESIDUES 282-879
Not recorded SO4 SULFATE ION × 3 RBQ (8S)-2-(morpholin-4-yl)-9-[2-(propan-2-yloxy)ethyl]-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one × 1 X-RAY DIFFRACTION
X-ray crystallization conditions pH 8.5；AMMONIUM SULFATE 2M - TRIS 100MM PH 8.5
Resolution 2.70 Å R-free 0.221
4UWH Discovery of (2S)-8-((3R)-3-Methylmorpholin-4-yl)-1-(3-methyl-2-oxo- butyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido(1,2-a)pyrimidin-6- one: a Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors Deposited 2014-08-12 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 282–879（598 aa） Fragment：VPS34 HELICAL AND KINASE DOMAINS, RESIDUES 282-879
Not recorded NA SODIUM ION × 2 JXM (8S)-9-[(2R)-2-hydroxy-2-phenylethyl]-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one × 1 X-RAY DIFFRACTION
X-ray crystallization conditions pH 7.5；NA CITRATE 1M PH8.0, pH 7.5
Resolution 1.93 Å R-free 0.208
4UWK Discovery of (2S)-8-((3R)-3-Methylmorpholin-4-yl)-1-(3-methyl-2-oxo- butyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido(1,2-a)pyrimidin-6- one: a Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors Deposited 2014-08-12 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 282–879（598 aa） Fragment：VPS34 HELICAL AND KINASE DOMAINS, UNP RESIDUES 282-879
Not recorded SO4 SULFATE ION × 1 GOL GLYCEROL × 1 UJB (2S)-1-[(5-chloro-2-thienyl)methyl]-8-[(3R,5R)-3,5-dimethylmorpholin-4-yl]-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido[1,2-a]pyrimidin-6-one × 1 X-RAY DIFFRACTION
X-ray crystallization conditions pH 8.5；AMMONIUM SULFATE 1.8M - TRIS 100MM PH 8.5
Resolution 2.83 Å R-free 0.225
4UWL Discovery of (2S)-8-((3R)-3-Methylmorpholin-4-yl)-1-(3-methyl-2-oxo- butyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido(1,2-a)pyrimidin-6- one: a Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors Deposited 2014-08-12 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 282–879（598 aa） Fragment：VPS34 HELICAL AND KINASE DOMAINS, RESIDUES 282-879
Not recorded SO4 SULFATE ION × 2 7A5 (8S)-2-[(3R)-3-methylmorpholin-4-yl]-9-(3-methyl-2-oxobutyl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one × 1 X-RAY DIFFRACTION
X-ray crystallization conditions pH 7.5；1.8M AMMONIUM SULFATE, 100MM TRIS PH 8
Resolution 2.80 Å R-free 0.255
5ANL Crystal structure of VPS34 in complex with (2S)-8-((3R)-3- Methylmorpholin-4-yl)-1-(3-methyl-2-oxo- butyl)-2-(trifluoromethyl)-3, 4-dihydro-2H-pyrimido(1,2-a)pyrimidin-6- one, processed with the CrystalDirect automated mounting and cryo-cooling technology Deposited 2015-09-07 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 282–879（598 aa） Fragment：VPS34 HELICAL AND KINASE DOMAINS, UNP RESIDUES 282-879
Not recorded RBQ (8S)-2-(morpholin-4-yl)-9-[2-(propan-2-yloxy)ethyl]-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one × 1 X-RAY DIFFRACTION
X-ray crystallization conditions 0.1 M TRIS, PH=7.5, 1.8 M AMMONIUM SULFATE
Resolution 2.70 Å R-free 0.267
5ENN The crystal structure of Human VPS34 in complex with a selective and potent inhibitor Deposited 2015-11-09 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 293–887（595 aa） Fragment：UNP residues 293-887
Not recorded 5QS 1-[[4-(cyclopropylmethyl)-5-[2-(pyridin-4-ylamino)pyrimidin-4-yl]pyrimidin-2-yl]amino]-2-methyl-propan-2-ol × 1 NA SODIUM ION × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 7.5；291.15 K；200nL:200nL well to protein 0.2M Sodium Acetate 0.1M HEPES 7.5 20% PEG 3000
Resolution 2.70 Å R-free 0.201
5ENN The crystal structure of Human VPS34 in complex with a selective and potent inhibitor Deposited 2015-11-09 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 293–887（595 aa） Fragment：UNP residues 293-887
Not recorded 5QS 1-[[4-(cyclopropylmethyl)-5-[2-(pyridin-4-ylamino)pyrimidin-4-yl]pyrimidin-2-yl]amino]-2-methyl-propan-2-ol × 1 NA SODIUM ION × 1 GOL GLYCEROL × 1 SO4 SULFATE ION × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 7.5；291.15 K；200nL:200nL well to protein 0.2M Sodium Acetate 0.1M HEPES 7.5 20% PEG 3000
Resolution 2.70 Å R-free 0.201
6HOG Structure of VPS34 LIR motif bound to GABARAP Deposited 2018-09-17 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Insufficient information Homooligomer；Protein × 3 PDB declaration: trimeric
Chain A 244–258（15 aa）
Not recorded SO4 SULFATE ION × 6 EDO 1,2-ETHANEDIOL × 6 GOL GLYCEROL × 6 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；293 K；50 mM HEPES pH 7.1, 40% PEG 600
Resolution 1.26 Å R-free 0.181
6HOH Structure of VPS34 LIR motif (S249E) bound to GABARAP Deposited 2018-09-17 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Insufficient information Homooligomer；Protein × 3 PDB declaration: trimeric
Chain A 244–258（15 aa）
Not recorded PGE TRIETHYLENE GLYCOL × 3 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；293 K；20% PEG 3350, 200 mM magnesium formate
Resolution 2.25 Å R-free 0.250
6HOH Structure of VPS34 LIR motif (S249E) bound to GABARAP Deposited 2018-09-17 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Insufficient information Homooligomer；Protein × 3 PDB declaration: trimeric
Chain B 244–258（15 aa）
Chain C 244–258（15 aa）
Chain D 244–258（15 aa）
Not recorded No recorded non-water small molecule X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；293 K；20% PEG 3350, 200 mM magnesium formate
Resolution 2.25 Å R-free 0.250
6YKG Structure-based exploration of selectivity for ATM inhibitors in Huntingtons disease Deposited 2020-04-06 Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain AAA 268–879（612 aa）
Not recorded OZ8 4-morpholin-4-yl-6-[(2~{R})-2-(phenylmethyl)pyrrolidin-1-yl]-1~{H}-pyridin-2-one × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 7；293 K；1.4 M sodium malonate pH 7.0, 0.1 M BIS-TRIS
Resolution 3.12 Å R-free 0.261
7BL1 human complex II-BATS bound to membrane-attached Rab5a-GTP Deposited 2021-01-17 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 BBB 1–887（887 aa）
Not recorded GTP GUANOSINE-5'-TRIPHOSPHATE × 1 MG MAGNESIUM ION × 1 ELECTRON MICROSCOPY
cryo-EM buffer pH 8
cryo-EM vitrification conditions Cryogen ETHANE；Blot force 20, blot time 6 s
Resolution 9.80 Å
7RSJ Structure of the VPS34 kinase domain with compound 14 Deposited 2021-08-11 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 282–879（598 aa）
Not recorded NA SODIUM ION × 3 7IH N-{4-[(7R,8R)-4-oxo-7-(propan-2-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl]pyridin-2-yl}cyclopropanecarboxamide × 1 EDO 1,2-ETHANEDIOL × 1 GOL GLYCEROL × 2 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；277.15 K；0.2M Potassium/Sodium tartrate 0.1M Bis-Tris propane pH7.5, 20% PEG3350 0.7% v/v 1-butanol
Resolution 1.88 Å R-free 0.203
7RSP Structure of the VPS34 kinase domain with compound 14 Deposited 2021-08-11 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 282–879（598 aa）
Not recorded GOL GLYCEROL × 1 7IK (7R,8R)-2-[(3R)-3-methylmorpholin-4-yl]-7-(propan-2-yl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；277.15 K；0.2M Potassium/Sodium tartrate, 0.1M Bis-Tris propane pH7.5, 20% PEG3350 0.7% v/v 1-butanol
Resolution 1.67 Å R-free 0.225
7RSP Structure of the VPS34 kinase domain with compound 14 Deposited 2021-08-11 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 282–879（598 aa）
Not recorded GOL GLYCEROL × 2 7IK (7R,8R)-2-[(3R)-3-methylmorpholin-4-yl]-7-(propan-2-yl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；277.15 K；0.2M Potassium/Sodium tartrate, 0.1M Bis-Tris propane pH7.5, 20% PEG3350 0.7% v/v 1-butanol
Resolution 1.67 Å R-free 0.225
7RSV Structure of the VPS34 kinase domain with compound 5 Deposited 2021-08-11 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 282–879（598 aa）
Not recorded 7IQ (5aS,8aR,9S)-2-[(3R)-3-methylmorpholin-4-yl]-5,5a,6,7,8,8a-hexahydro-4H-cyclopenta[e]pyrazolo[1,5-a]pyrazin-4-one × 1 GOL GLYCEROL × 2 NA SODIUM ION × 4 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；277.15 K；0.2M Potassium/Sodium tartrate 0.1M Bis-Tris propane pH7.5, 20% PEG3350 0.7% v/v 1-butanol
Resolution 1.78 Å R-free 0.214
7RSV Structure of the VPS34 kinase domain with compound 5 Deposited 2021-08-11 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 282–879（598 aa）
Not recorded 7IQ (5aS,8aR,9S)-2-[(3R)-3-methylmorpholin-4-yl]-5,5a,6,7,8,8a-hexahydro-4H-cyclopenta[e]pyrazolo[1,5-a]pyrazin-4-one × 1 GOL GLYCEROL × 1 NA SODIUM ION × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；277.15 K；0.2M Potassium/Sodium tartrate 0.1M Bis-Tris propane pH7.5, 20% PEG3350 0.7% v/v 1-butanol
Resolution 1.78 Å R-free 0.214
8RXR Crystal structure of VPS34 in complex with inhibitor SB02024 Deposited 2024-02-07 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 282–879（598 aa）
Not recorded A1H4E 4-[(3R)-3-methylmorpholin-4-yl]-2-[(2R)-2-(trifluoromethyl)piperidin-1-yl]-3H-pyridin-6-one × 1 PEG DI(HYDROXYETHYL)ETHER × 2 IMD IMIDAZOLE × 1 DMS DIMETHYL SULFOXIDE × 3 GOL GLYCEROL × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8；277 K；22.5 % PEG3350, 0.2 M ammonium acetate, 0.1 M HEPES pH 8.0
Resolution 2.06 Å R-free 0.225
8RXR Crystal structure of VPS34 in complex with inhibitor SB02024 Deposited 2024-02-07 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 282–879（598 aa）
Not recorded A1H4E 4-[(3R)-3-methylmorpholin-4-yl]-2-[(2R)-2-(trifluoromethyl)piperidin-1-yl]-3H-pyridin-6-one × 1 DMS DIMETHYL SULFOXIDE × 5 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8；277 K；22.5 % PEG3350, 0.2 M ammonium acetate, 0.1 M HEPES pH 8.0
Resolution 2.06 Å R-free 0.225
9C82 Structure of human ULK1C:PI3KC3-C1 supercomplex Deposited 2024-06-11 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 × 5 PDB declaration: pentameric
Chain B 1–887（887 aa）
Not recorded No recorded non-water small molecule ELECTRON MICROSCOPY
cryo-EM buffer pH 7.5
cryo-EM vitrification conditions Cryogen ETHANE；added 0.05% (w/v) octylglucopyranoside as surfactant
Resolution 6.84 Å
9DKP The structure of human vacuolar protein sorting 34 catalytic domain bound to RD-I-53 Deposited 2024-09-09 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 290–871（582 aa）
Not recorded A1A6F (8R)-3-(1,3-benzothiazol-2-yl)pyrazolo[1,5-a]pyrimidine × 1 ETX 2-ETHOXYETHANOL × 1 ETZ diethyl ether × 2 DMS DIMETHYL SULFOXIDE × 1 K POTASSIUM ION × 2 CL CHLORIDE ION × 13 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION；pH 6；298 K；20% PEG, 0.2M MES pH 6.0
Resolution 2.16 Å R-free 0.235
9E4V The structure of human vacuolar protein sorting 34 catalytic domain bound to MES Deposited 2024-10-25 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 290–871（582 aa）
Not recorded MES 2-(N-MORPHOLINO)-ETHANESULFONIC ACID × 1 PG4 TETRAETHYLENE GLYCOL × 1 DMS DIMETHYL SULFOXIDE × 1 PEG DI(HYDROXYETHYL)ETHER × 4 GOL GLYCEROL × 1 CL CHLORIDE ION × 4 K POTASSIUM ION × 3 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION；pH 6；298 K；100mM MES, pH 6.0, 18% PEG3350
Resolution 2.36 Å R-free 0.231
9MHF Cryo-EM reconstruction of PI3KC3-C1 in complex with Human RAB1A(Q70L) Deposited 2024-12-11 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 × 5 PDB declaration: pentameric
Chain B 1–887（887 aa）
Not recorded GTP GUANOSINE-5'-TRIPHOSPHATE × 2 MG MAGNESIUM ION × 2 MYR MYRISTIC ACID × 1 ELECTRON MICROSCOPY
cryo-EM buffer pH 7.4
cryo-EM vitrification conditions Cryogen ETHANE
Resolution 2.73 Å
9MHG Cryo EM reconstruction of PI3KC3-C1 in complex with Human RAB1A(Q70L), VPS34 kinase domain in the inactive conformation Deposited 2024-12-11 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 × 5 PDB declaration: pentameric
Chain B 1–887（887 aa）
Not recorded GTP GUANOSINE-5'-TRIPHOSPHATE × 2 MG MAGNESIUM ION × 2 MYR MYRISTIC ACID × 1 ELECTRON MICROSCOPY
cryo-EM buffer pH 7.4；OG supplemented at time of grid preparation 0.05%
cryo-EM vitrification conditions Cryogen ETHANE；100% humidity, 3 s wait time, blot force -15
Resolution 3.20 Å
9MHH PI3KC3-C1 in complex with RAB1A. VPS34 kinase domain active conformation Deposited 2024-12-11 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 × 5 PDB declaration: pentameric
Chain B 1–887（887 aa）
Not recorded GTP GUANOSINE-5'-TRIPHOSPHATE × 2 MG MAGNESIUM ION × 2 ELECTRON MICROSCOPY
cryo-EM buffer pH 7.4；OG supplemented at time of grid preparation 0.05%
cryo-EM vitrification conditions Cryogen ETHANE
Resolution 4.50 Å
9NIN The structure of human Vacuolar Protein Sorting 34 catalytic domain bound to RD-I-86 Deposited 2025-02-26 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 290–871（582 aa）
Not recorded A1BYW 2-[(8R)-pyrazolo[1,5-a]pyrimidin-3-yl]-1,3-benzothiazol-6-ol × 1 ACT ACETATE ION × 2 EDO 1,2-ETHANEDIOL × 4 PEG DI(HYDROXYETHYL)ETHER × 1 CL CHLORIDE ION × 14 K POTASSIUM ION × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION；pH 6；298 K；0.1 M Ammonium acetate, 0.1 M BIS-TRIS pH 5.5, 17% w/v Polyethylene glycol 10,000
Resolution 2.01 Å R-free 0.212
9ORM The structure of human Vacuolar Protein Sorting 34 catalytic domain bound to RD-I-137 Deposited 2025-05-22 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 290–871（582 aa）
Not recorded A1CD6 ethyl 2-[(8S)-pyrazolo[1,5-a]pyrimidin-3-yl]-1,3-benzothiazole-6-carboxylate × 1 GOL GLYCEROL × 2 PEG DI(HYDROXYETHYL)ETHER × 2 CL CHLORIDE ION × 6 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION；pH 6；298 K；0.1 M Ammonium acetate, 0.1 M BIS-TRIS pH 5.5, 17% w/v Polyethylene glycol 10,000
Resolution 2.06 Å R-free 0.227
9RX5 VPS34-CII (VPS34 199-REIE-202 to 199-AAAA-202 mutant) bound to RAB5A (Q79L) Deposited 2025-07-10 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 1–887（887 aa）
Mutation：199-REIE-202 to 199-AAAA-202 No recorded non-water small molecule ELECTRON MICROSCOPY mmCIF provides none of the parsed conditions Resolution 3.15 Å
9RX6 VPS34-CII (VPS34 199-REIE-202 to 199-ERIR-202 mutant) bound to RAB5A (Q79L) on the VPS15 subunit Deposited 2025-07-10 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 × 5 PDB declaration: pentameric
Chain A 1–887（887 aa）
Mutation：199-REIE-202 to 199-ERIR-202 No recorded non-water small molecule ELECTRON MICROSCOPY mmCIF provides none of the parsed conditions Resolution 3.52 Å
9RX8 Apo VPS34-CII (VPS34/VPS15/BECLIN1/UVRAG) Deposited 2025-07-10 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 1–887（887 aa）
Not recorded No recorded non-water small molecule ELECTRON MICROSCOPY mmCIF provides none of the parsed conditions Resolution 3.87 Å
9RX9 VPS34-CII bound to RAB5A-GTP 1-212 (C19S, C63S, Q79L) on the VPS34 subunit Deposited 2025-07-10 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 × 5 PDB declaration: pentameric
Chain A 1–887（887 aa）
Not recorded No recorded non-water small molecule ELECTRON MICROSCOPY mmCIF provides none of the parsed conditions Resolution 3.99 Å
9RXA VPS34-CII bound to RAB5A-GTP 1-212 (C19S, C63S, Q79L) on the VPS15 subunit Deposited 2025-07-10 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 × 5 PDB declaration: pentameric
Chain A 1–887（887 aa）
Not recorded No recorded non-water small molecule ELECTRON MICROSCOPY mmCIF provides none of the parsed conditions Resolution 4.00 Å
9RXB VPS34-CII (VPS34/VPS15/BECLIN1/UVRAG) bound to RAB5A (Q79L) on the VPS34 and VPS15 subunits Deposited 2025-07-10 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 1–887（887 aa）
Not recorded No recorded non-water small molecule ELECTRON MICROSCOPY mmCIF provides none of the parsed conditions Resolution 4.03 Å
9S47 Human complex II-BATS bound to membrane-attached Rab5a-GTP Deposited 2025-07-25 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 × 5 PDB declaration: pentameric
Chain A 1–887（887 aa）
Not recorded No recorded non-water small molecule ELECTRON MICROSCOPY mmCIF provides none of the parsed conditions Resolution 9.88 Å
9ZF4 The structure of human Vacuolar Protein Sorting 34 catalytic domain bound to RD-II-83 Deposited 2025-12-01 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 290–871（582 aa）
Not recorded A1C15 methyl 2-[(8R)-pyrazolo[1,5-a]pyrimidin-3-yl]-1,3-benzothiazole-6-carboxylate × 1 GOL GLYCEROL × 1 PEG DI(HYDROXYETHYL)ETHER × 5 DMS DIMETHYL SULFOXIDE × 1 MG MAGNESIUM ION × 2 CL CHLORIDE ION × 2 K POTASSIUM ION × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 6.5；297 K；0.2 M Sodium Chloride, 25% w/v Polyethylene glycol 3,350
Resolution 2.09 Å R-free 0.224
9ZPC Cryo-EM structure of human PI3KC3-C2 Deposited 2025-12-16 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 B 1–887（887 aa）
Not recorded GDP GUANOSINE-5'-DIPHOSPHATE × 1 MG MAGNESIUM ION × 1 ZN ZINC ION × 1 ELECTRON MICROSCOPY
cryo-EM buffer pH 7.5
cryo-EM vitrification conditions Cryogen ETHANE
Resolution 3.83 Å
9ZPD Cryo-EM structure of human PI3KC3-C2 in complex with Rubicon Middle Region of C terminus Deposited 2025-12-16 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics Assembly 1 Insufficient information Heteromer；Protein × 5 PDB declaration: pentameric
Chain B 1–887（887 aa）
Not recorded GTP GUANOSINE-5'-TRIPHOSPHATE × 1 ZN ZINC ION × 1 ELECTRON MICROSCOPY
cryo-EM buffer pH 7.5
cryo-EM vitrification conditions Cryogen ETHANE
Resolution 3.38 Å

40 other PDB entries and 50 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name PK3C3_HUMAN
Isoform —
PDB entities 1
Chains and sequence ranges Author chain A； PDBConstruct 3–615； UniProt 268–879

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 6i3u

P(r) Distance Distribution P(r) Distribution

P(r) distribution for 6i3u
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2. Structure Basics 2. Structure Basics

Entry ID entry_id6i3u
Deposition date deposition_date2018-11-07
Structure title titleOptimization of potent and selective ATM inhibitors suitable for a proof-of-concept study in Huntington's disease models
Keywords keywords;ATM surrogate, VPS34, Kinase, Huntington's disease, LYASE ;; LYASE
Experimental Method methodX-RAY DIFFRACTION
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3. SAXS Parameters (CRYSOL theoretical calculation) 3. SAXS Parameters (CRYSOL)

Radius of gyration Rg (Guinier) rg_guinier26.96 Å
Radius of gyration Rg (electron density) rg_electron25.67 Å
Forward intensity I(0) i063580200.00
Molecular weight molecular_weight63285.0 kDa
Excluded volume excluded_volume79702 ų
Envelope volume envelope_volume95557 ų
Hydration-shell volume shell_volume31006 ų
Envelope diameter envelope_diameter88.8 Å
Shell Rg shell_rg33.02 Å
Envelope Rg envelope_rg25.93 Å
Shape Rg shape_rg25.69 Å
Total Rg total_rg26.42 Å
Total atoms total_atoms4455
Residues n_residues557
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 dmax85.7 Å
Rg (real space) rg_real26.89 Å
Rg uncertainty (real space) rg_real_error0.55 Å
I(0) (real space) i0_real6.3580e+07
I(0) uncertainty (real space) i0_real_error8.7200e+05
Rg (reciprocal space) rg_reciprocal26.91 Å
I(0) (reciprocal space) i0_reciprocal63580000.0000
Solution quality estimate total_estimate0.9016
Solution quality rating solution_quality EXCELLENT a EXCELLENT solution
P(r) peaks n_peaks2
Primary peak position r_peak_primary31.9 Å
Skewness Skewness skewness0.268
Kurtosis Kurtosis kurtosis-0.404
Angular range angular_range— – 0.2950 Å−1
Current regularization parameter α current_alpha0.0000
Highest regularization parameter α highest_alpha15780000.0000
Real-space data points n_real_points60
GNOM version gnom_version4.1.3
Quality Criteria quality_criteria AN1: 0.000; Oscil: 0.924; Stabil: 1.000; Sysdev: 1.000; Positv: 1.000; Valcen: 0.997; Smooth: 0.947
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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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7. Fold Classification (SCOP + CATH) 2 domains

CATH v4.4 (2 domains)

Domain ID domain_id6i3uA01
Class class3 — Alpha Beta
Architecture architecture30 — 2-Layer Sandwich
Topology topology1010 — Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 4
Homologous superfamily homologous superfamily10 — Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 4
Domain ID domain_id6i3uA02
Class class1 — Mainly Alpha
Architecture architecture10 — Orthogonal Bundle
Topology topology1070 — Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, Domain 5
Homologous superfamily homologous superfamily11 — Phosphatidylinositol 3-/4-kinase, catalytic domain
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8. Citations (1)

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9. Files and Curves (10)