Structure of PDB 4uwl Chain A Binding Site BS01

Receptor Information
>4uwl Chain A (length=543) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
LKPNAATRDQLNIIVSYPPTKQLTYEEQDLVWKFRYYLTNQEKALTKFLK
CVNWDLPQEAKQALELLGKWKPMDVEDSLELLSSHYTNPTVRRYAVARLR
QADDEDLLMYLLQLVQALKYENFDDIKNGLEEIDSSQIITSPLPLEQDLC
TFLISRACKNSTLANYLYWYVIVECEDQDTQQRDPKTHEMYLNVMRRFSQ
ALLKGDKSVRVMRSLLAAQQTFVDRLVHLMKAVQRESGNRKKKNERLQAL
LGDNEKMNLSDVELIPLPLEPQVKIRGIIPETATLFKSALMPAQLFFKTE
DGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATS
TKHGFMQFIQSVPVAEVLDTEGSIQNFFRKYAPSENGPNGISAEVMDTYV
KSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILGRDPKPLPPP
MKLNKEMVEGMGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDA
NIPDIALEPDKTVKKVQDKFRLDLSDEEAVHYMQSLIDESVHA
Ligand information
Ligand ID7A5
InChIInChI=1S/C18H25F3N4O3/c1-11(2)13(26)9-25-14(18(19,20)21)4-5-24-16(27)8-15(22-17(24)25)23-6-7-28-10-12(23)3/h8,11-12,14H,4-7,9-10H2,1-3H3/t12-,14+/m1/s1
InChIKeyITCIAOUZMPREOO-OCCSQVGLSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6C[C@@H]1COCCN1C2=CC(=O)N3CC[C@H](N(C3=N2)CC(=O)C(C)C)C(F)(F)F
CACTVS 3.385CC(C)C(=O)CN1[CH](CCN2C(=O)C=C(N=C12)N3CCOC[CH]3C)C(F)(F)F
OpenEye OEToolkits 1.7.6CC1COCCN1C2=CC(=O)N3CCC(N(C3=N2)CC(=O)C(C)C)C(F)(F)F
CACTVS 3.385CC(C)C(=O)CN1[C@@H](CCN2C(=O)C=C(N=C12)N3CCOC[C@H]3C)C(F)(F)F
ACDLabs 12.01FC(F)(F)C3N(C2=NC(N1C(COCC1)C)=CC(=O)N2CC3)CC(=O)C(C)C
FormulaC18 H25 F3 N4 O3
Name(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
ChEMBLCHEMBL4586628
DrugBank
ZINCZINC000210833955
PDB chain4uwl Chain A Residue 1872 [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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PDB4uwl 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.
Resolution2.8 Å
Binding residue
(original residue number in PDB)		F612 S614 P618 I634 Y670 M682 Q683 F684 I685 I760 D761
Binding residue
(residue number reindexed from 1)		F286 S288 P292 I308 Y344 M356 Q357 F358 I359 I434 D435
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=8.57,Kd=2.7nM
BindingDB: IC50=82nM
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:4uwl, PDBe:4uwl, PDBj:4uwl
PDBsum4uwl
PubMed25402320
UniProtQ8NEB9|PK3C3_HUMAN Phosphatidylinositol 3-kinase catalytic subunit type 3 (Gene Name=PIK3C3)

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