Structure of PDB 4uwh Chain A Binding Site BS01

Receptor Information
>4uwh Chain A (length=554) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
DLKPNAATRDQLNIIVSYPPTKQLTYEEQDLVWKFRYYLTNQEKALTKFL
KCVNWDLPQEAKQALELLGKWKPMDVEDSLELLSSHYTNPTVRRYAVARL
RQADDEDLLMYLLQLVQALKYENFDDIKNGLEPINSAEIDSSQIITSPLP
NLEQDLCTFLISRACKNSTLANYLYWYVIVECEDQDTQQRDPKTHEMYLN
VMRRFSQALLKGDKSVRVMRSLLAAQQTFVDRLVHLMKAVQRESGNRKKK
NERLQALLGDNEKMNLSDVELIPLPLEPQVKIRGIIPETATLFKSALMPA
QLFFKTEDGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKLTP
YKVLATSTKHGFMQFIQSVPVAEVLDTEGSIQNFFRKYAPSENGPNGISA
EVMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILGRD
PKPLPPPMKLNKEMVEGMGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNL
FSLMVDANIPDIALEPDKTVKKVQDKFRLDLSDEEAVHYMQSLIDESVHA
LFAA
Ligand information
Ligand IDJXM
InChIInChI=1S/C20H23F3N4O3/c21-20(22,23)16-6-7-26-18(29)12-17(25-8-10-30-11-9-25)24-19(26)27(16)13-15(28)14-4-2-1-3-5-14/h1-5,12,15-16,28H,6-11,13H2/t15-,16-/m0/s1
InChIKeyPZFUMOISBVVUGC-HOTGVXAUSA-N
SMILES
SoftwareSMILES
CACTVS 3.385O[CH](CN1[CH](CCN2C(=O)C=C(N=C12)N3CCOCC3)C(F)(F)F)c4ccccc4
OpenEye OEToolkits 1.7.6c1ccc(cc1)C(CN2C(CCN3C2=NC(=CC3=O)N4CCOCC4)C(F)(F)F)O
ACDLabs 12.01FC(F)(F)C3N(C2=NC(N1CCOCC1)=CC(=O)N2CC3)CC(O)c4ccccc4
CACTVS 3.385O[C@@H](CN1[C@@H](CCN2C(=O)C=C(N=C12)N3CCOCC3)C(F)(F)F)c4ccccc4
OpenEye OEToolkits 1.7.6c1ccc(cc1)[C@H](CN2[C@@H](CCN3C2=NC(=CC3=O)N4CCOCC4)C(F)(F)F)O
FormulaC20 H23 F3 N4 O3
Name(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
ChEMBLCHEMBL4536755
DrugBank
ZINCZINC000114867562
PDB chain4uwh Chain A Residue 1876 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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PDB4uwh 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.
Resolution1.93 Å
Binding residue
(original residue number in PDB)		F612 P618 I634 K636 Y670 M682 Q683 F684 I685 L750 I760
Binding residue
(residue number reindexed from 1)		F293 P299 I315 K317 Y351 M363 Q364 F365 I366 L431 I441
Annotation score1
Binding affinityMOAD: ic50=3nM
PDBbind-CN: -logKd/Ki=8.52,IC50=3nM
BindingDB: IC50=3.0nM
Enzymatic activity
Enzyme Commision number 2.7.1.137: phosphatidylinositol 3-kinase.
Gene Ontology
Molecular Function
GO:0016301 kinase activity
Biological Process
GO:0046854 phosphatidylinositol phosphate biosynthetic process

View graph for
Molecular Function
View graph for
Biological Process
External links
PDB RCSB:4uwh, PDBe:4uwh, PDBj:4uwh
PDBsum4uwh
PubMed25402320
UniProtQ8NEB9|PK3C3_HUMAN Phosphatidylinositol 3-kinase catalytic subunit type 3 (Gene Name=PIK3C3)

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