Structure of PDB 5vlr Chain A Binding Site BS01

Receptor Information
>5vlr Chain A (length=926) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
NQSVVVDFLLPTGVYLNFPVSRNANLSTIKQLLWHRAQYEPLFHMLSGPE
AYVFTCINQTAEQQELEDEQRRLCDVQPFLPVLRLVAREGDRVKKLINSQ
ISLLIGKGLHEFDSLCDPEVNDFRAKMCQFCEEAAARRQQLGWEAWLQYS
FPLQLEPSLPNRALLVNVKFEGSEESFTFQVSTKDVPLALMACALRKKAT
EDYTLQVNGRHEYLYGSYPLCQFQYICSCLHSGLTPHLTMVHSSSILAMR
DLWSLEQPFRIELIQGSKVNADERMKLVVQAGLFHGNEMLCKTVSSSEVS
VCSEPVWKQRLEFDINICDLPRMARLCFALYAVIEKAKADCPIAWANLML
FDYKDQLKTGERCLYMWPSVPDEKGELLNPTGTVRSNPNTDSAAALLICL
PEVAPHPVYYPALEKILELGRHTEEEQLQLREILEGELYEHEKDLVWKLR
HEVQEHFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLDF
SFPDCHVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLD
RALANRKIGHFLFWHLRSEMHVPSVALRFGLILEAYCRGSTHHMKVLMKQ
GEALSKLKALNDFVKLSSQKTPKPQTKELMHLCMRQEAYLEALSHLQSPL
DPSTLLAEVCVEQCTFMDSKMKPLWIMYSNEEASVGIIFKNGDDLRQDML
TLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLRSDTIANIQL
NFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDN
IMIRESGQLFHIDFGHFLGNFINRERVPFILTYDFVHVIQQGKTNNSEKF
ERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLA
LGKTEEEALKHFRVKFNEALRESWKT
Ligand information
Ligand ID9EM
InChIInChI=1S/C25H25F3N8O2/c1-15(37)34-10-9-33(23(38)24(34,2)3)17-6-4-5-16(11-17)20-12-18(21-22(29)30-14-32-36(20)21)19-7-8-31-35(19)13-25(26,27)28/h4-8,11-12,14H,9-10,13H2,1-3H3,(H2,29,30,32)
InChIKeyKSAKMNJFOKNIAA-UHFFFAOYSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 2.0.6CC(=O)N1CCN(C(=O)C1(C)C)c2cccc(c2)c3cc(c4n3ncnc4N)c5ccnn5CC(F)(F)F
ACDLabs 12.01CC1(C)C(=O)N(CCN1C(=O)C)c2cccc(c2)c3cc(c4n3ncnc4N)c5ccnn5CC(F)(F)F
CACTVS 3.385CC(=O)N1CCN(c2cccc(c2)c3cc(c4ccnn4CC(F)(F)F)c5n3ncnc5N)C(=O)C1(C)C
FormulaC25 H25 F3 N8 O2
Name4-acetyl-1-(3-{4-amino-5-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl]pyrrolo[2,1-f][1,2,4]triazin-7-yl}phenyl)-3,3-dimethylpiperazin-2-one
ChEMBLCHEMBL4059848
DrugBank
ZINC
PDB chain5vlr Chain A Residue 4001 [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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PDB5vlr Identification of a Potent, Selective, and Efficacious Phosphatidylinositol 3-Kinase delta (PI3K delta ) Inhibitor for the Treatment of Immunological Disorders.
Resolution2.8 Å
Binding residue
(original residue number in PDB)		T750 M752 W760 I777 K779 Y813 I825 E826 V828 T833 M900 I910 D911
Binding residue
(residue number reindexed from 1)		T665 M667 W675 I688 K690 Y724 I736 E737 V739 T744 M802 I812 D813
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=8.52,IC50=3nM
BindingDB: IC50=3.00nM
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:5vlr, PDBe:5vlr, PDBj:5vlr
PDBsum5vlr
PubMed28541707
UniProtO00329|PK3CD_HUMAN Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (Gene Name=PIK3CD)

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