Structure of PDB 6pyu Chain A Binding Site BS01

Receptor Information
>6pyu Chain A (length=930) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
NQSVVVDFLLPTGVYLNFPVSRNANLSTIKQLLWHRAQYEPLFHMLSGPE
AYVFTCINQTAEQQELEDEQRRLCDVQPFLPVLRLVAREGDRVKKLINSQ
ISLLIGKGLHEFDSLCDPEVNDFRAKMCQFCEEAAARRQQLGWEAWLQYS
FPLQLEPSAPNRALLVNVKFEGSEESFTFQVSTKDVPLALMACALRKKAT
QPEDYTLQVNGRHEYLYGSYPLCQFQYICSCLHSGLTPHLTMVHSSSILA
MRDEVSLWSLEQPFRIELIQGSKVNADERMKLVVQAGLFHGNEMLCKTVS
SSEVSVCSEPVWKQRLEFDINICDLPRMARLCFALYAVIEDCPIAWANLM
LFDYKDQLKTGERCLYMWPSVPDEKGELLNPTGTVRSNPNTDSAAALLIC
LPEVAPHPVYYPALEKILELGRHSEEEQLQLREILERGELYEHEKDLVWK
LRHEVQEHFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELL
DFSFPDCHVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFL
LDRALANRKIGHFLFWHLRSEMHVPSVALRFGLILEAYCRGSTHHMKVLM
KQGEALSKLKALNDFVKLSSQKTPKPQTKELMHLCMRQEAYLEALSHLQS
PLDPSTLLAEVCVEQCTFMDSKMKPLWIMYSNEEAGSGGSVGIIFKNGDD
LRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLRSDT
IANIQLKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRH
SDNIMIRESGQLFHIDFGHFLGNERVPFILTYDFVHVIQQGKTNNSEKFE
RFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLAL
GKTEEEALKHFRVKFNEALRESWKTKVNWL
Ligand information
Ligand IDP5V
InChIInChI=1S/C23H20N4O2/c28-21(14-2-3-14)27-11-1-8-23(27)17-12-15(4-6-18(17)26-22(23)29)16-5-7-19-20(13-16)25-10-9-24-19/h4-7,9-10,12-14H,1-3,8,11H2,(H,26,29)/t23-/m0/s1
InChIKeyPXPGVPPGCPSCSN-QHCPKHFHSA-N
SMILES
SoftwareSMILES
CACTVS 3.385O=C1Nc2ccc(cc2[C@@]13CCCN3C(=O)C4CC4)c5ccc6nccnc6c5
OpenEye OEToolkits 2.0.7c1cc2c(cc1c3ccc4c(c3)C5(CCCN5C(=O)C6CC6)C(=O)N4)nccn2
ACDLabs 12.01C2(=O)Nc1ccc(cc1C24CCCN4C(=O)C3CC3)c5cc6c(cc5)nccn6
OpenEye OEToolkits 2.0.7c1cc2c(cc1c3ccc4c(c3)[C@@]5(CCCN5C(=O)C6CC6)C(=O)N4)nccn2
CACTVS 3.385O=C1Nc2ccc(cc2[C]13CCCN3C(=O)C4CC4)c5ccc6nccnc6c5
FormulaC23 H20 N4 O2
Name(3S)-1'-(cyclopropanecarbonyl)-5-(quinoxalin-6-yl)spiro[indole-3,2'-pyrrolidin]-2(1H)-one
ChEMBLCHEMBL4524356
DrugBank
ZINC
PDB chain6pyu Chain A Residue 1101 [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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PDB6pyu Design of selective PI3K delta inhibitors using an iterative scaffold-hopping workflow.
Resolution2.54 Å
Binding residue
(original residue number in PDB)		T750 W760 Y813 I825 E826 V828 N836 M900
Binding residue
(residue number reindexed from 1)		T667 W677 Y730 I742 E743 V745 N753 M805
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=8.00,IC50=10nM
BindingDB: IC50=10.0nM
Enzymatic activity
Enzyme Commision number 2.7.1.137: phosphatidylinositol 3-kinase.
2.7.1.153: phosphatidylinositol-4,5-bisphosphate 3-kinase.
Gene Ontology
Molecular Function
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016303 1-phosphatidylinositol-3-kinase activity
GO:0035005 1-phosphatidylinositol-4-phosphate 3-kinase activity
GO:0046934 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity
Biological Process
GO:0001779 natural killer cell differentiation
GO:0001819 positive regulation of cytokine production
GO:0001938 positive regulation of endothelial cell proliferation
GO:0002250 adaptive immune response
GO:0002551 mast cell chemotaxis
GO:0002679 respiratory burst involved in defense response
GO:0006468 protein phosphorylation
GO:0006629 lipid metabolic process
GO:0006935 chemotaxis
GO:0006954 inflammatory response
GO:0006955 immune response
GO:0007165 signal transduction
GO:0010595 positive regulation of endothelial cell migration
GO:0010628 positive regulation of gene expression
GO:0010818 T cell chemotaxis
GO:0016310 phosphorylation
GO:0030101 natural killer cell activation
GO:0030154 cell differentiation
GO:0030183 B cell differentiation
GO:0030217 T cell differentiation
GO:0030335 positive regulation of cell migration
GO:0030593 neutrophil chemotaxis
GO:0033031 positive regulation of neutrophil apoptotic process
GO:0035747 natural killer cell chemotaxis
GO:0035754 B cell chemotaxis
GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process
GO:0038084 vascular endothelial growth factor signaling pathway
GO:0042110 T cell activation
GO:0042113 B cell activation
GO:0043303 mast cell degranulation
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction
GO:0045087 innate immune response
GO:0045766 positive regulation of angiogenesis
GO:0046854 phosphatidylinositol phosphate biosynthetic process
GO:0048015 phosphatidylinositol-mediated signaling
GO:0050852 T cell receptor signaling pathway
GO:0050853 B cell receptor signaling pathway
GO:0060374 mast cell differentiation
GO:0072672 neutrophil extravasation
GO:1905278 positive regulation of epithelial tube formation
Cellular Component
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005942 phosphatidylinositol 3-kinase complex
GO:0005943 phosphatidylinositol 3-kinase complex, class IA

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Molecular Function
View graph for
Biological Process
View graph for
Cellular Component
External links
PDB RCSB:6pyu, PDBe:6pyu, PDBj:6pyu
PDBsum6pyu
PubMed31416665
UniProtO00329|PK3CD_HUMAN Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (Gene Name=PIK3CD)

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