Structure of PDB 8tsc Chain A Binding Site BS01
Receptor Information
>8tsc Chain A (length=1008) Species:
9606
(Homo sapiens) [
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PSSGELWGIHLMPPRILVECLLPNGMIVTLECLREATLITIKHELFKEAR
KYPLHQLLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEP
VGNREEKILNREIGFAIGMPVCEFDMVKDPEVQDFRRNILNVCKEAVDLR
DLNSPHSRAMYVYPPNVESSPELPKHIYNKLDKGQIIVVIWVIVSPNNDK
QKYTLKINHDCVPEQVIAEAIRKKTRSMLLSSEQLKLCVLEYQGKYILKV
CGCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKESLYSQLPMDCFTM
PSYSRRISSTKSLWVINSALRIKILCATYVNVNIRDIDKIYVRTGIYHGG
EPLCDNVNTQRVPCSNPRWNEWLNYDIYIPDLPRAARLCLSICSVKGRKG
AKEEHCPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGS
NPNKETPCLELEFDWFSSVVKFPDMSVIEEHANWSVSRLRENDKEQLKAI
STRDPLSEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMY
CLVKDWPPIKPEQAMELLDCNYPDPMVRGFAVRCLEKYLTDDKLSQYLIQ
LVQVLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNKTVSQRF
GLLLESYCRACGMYLKHLNRQVEAMEKLINLTDILKQEKKDETQKVQMKF
LVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLWLNWE
NPDIMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRML
PYGCLSIGDCVGLIEVVRNSHTIMQIQCKGGLKGALQFNSHTLHQWLKDK
NKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDF
GHFLDHKKRVPFVLTQDFLIVISKGAQECTKTREFERFQEMCYKAYLAIR
QHANLFINLFSMMLGSGMPELQSFDDIAYIRKTLALDKTEQEALEYFMKQ
MNDARHGG
Ligand information
Ligand ID
UJC
InChI
InChI=1S/C25H19F4N3O3/c1-12-5-3-4-6-17(12)21-20-18(24(35)32-21)9-14(22(33)30-2)10-19(20)31-23(34)13-7-15(25(27,28)29)11-16(26)8-13/h3-11,21H,1-2H3,(H,30,33)(H,31,34)(H,32,35)/t21-/m0/s1
InChIKey
CIGJKSFOADUAIC-NRFANRHFSA-N
SMILES
Software
SMILES
OpenEye OEToolkits 2.0.7
Cc1ccccc1[C@H]2c3c(cc(cc3NC(=O)c4cc(cc(c4)F)C(F)(F)F)C(=O)NC)C(=O)N2
ACDLabs 12.01
FC(F)(F)c1cc(cc(F)c1)C(=O)Nc1cc(cc2C(=O)NC(c21)c1ccccc1C)C(=O)NC
CACTVS 3.385
CNC(=O)c1cc(NC(=O)c2cc(F)cc(c2)C(F)(F)F)c3[CH](NC(=O)c3c1)c4ccccc4C
OpenEye OEToolkits 2.0.7
Cc1ccccc1C2c3c(cc(cc3NC(=O)c4cc(cc(c4)F)C(F)(F)F)C(=O)NC)C(=O)N2
CACTVS 3.385
CNC(=O)c1cc(NC(=O)c2cc(F)cc(c2)C(F)(F)F)c3[C@@H](NC(=O)c3c1)c4ccccc4C
Formula
C25 H19 F4 N3 O3
Name
(1S)-7-[3-fluoro-5-(trifluoromethyl)benzamido]-N-methyl-1-(2-methylphenyl)-3-oxo-2,3-dihydro-1H-isoindole-5-carboxamide
ChEMBL
DrugBank
ZINC
PDB chain
8tsc Chain A Residue 1101 [
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Receptor-Ligand Complex Structure
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PDB
8tsc
Discovery and clinical proof-of-concept of RLY-2608, a first-in-class mutant-selective allosteric PI3Ka inhibitor that decouples anti-tumor activity from hyperinsulinemia.
Resolution
3.62 Å
Binding residue
(original residue number in PDB)
Q809 L911 G912 L938 F1002 E1012 D1018 Y1021
Binding residue
(residue number reindexed from 1)
Q775 L877 G878 L904 F960 E970 D976 Y979
Annotation score
1
Enzymatic activity
Enzyme Commision number
2.7.11.1
: non-specific serine/threonine protein kinase.
2.7.1.137
: phosphatidylinositol 3-kinase.
2.7.1.153
: phosphatidylinositol-4,5-bisphosphate 3-kinase.
Gene Ontology
Molecular Function
GO:0004674
protein serine/threonine kinase activity
GO:0005515
protein binding
GO:0005524
ATP binding
GO:0016301
kinase activity
GO:0016303
1-phosphatidylinositol-3-kinase activity
GO:0030295
protein kinase activator activity
GO:0035005
1-phosphatidylinositol-4-phosphate 3-kinase activity
GO:0043560
insulin receptor substrate binding
GO:0044024
histone H2AS1 kinase activity
GO:0046934
1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity
GO:0106310
protein serine kinase activity
Biological Process
GO:0001525
angiogenesis
GO:0001889
liver development
GO:0001944
vasculature development
GO:0006006
glucose metabolic process
GO:0006629
lipid metabolic process
GO:0006909
phagocytosis
GO:0007173
epidermal growth factor receptor signaling pathway
GO:0008286
insulin receptor signaling pathway
GO:0010468
regulation of gene expression
GO:0010592
positive regulation of lamellipodium assembly
GO:0010629
negative regulation of gene expression
GO:0014823
response to activity
GO:0014870
response to muscle inactivity
GO:0016242
negative regulation of macroautophagy
GO:0016310
phosphorylation
GO:0030036
actin cytoskeleton organization
GO:0030168
platelet activation
GO:0030835
negative regulation of actin filament depolymerization
GO:0031295
T cell costimulation
GO:0032008
positive regulation of TOR signaling
GO:0032869
cellular response to insulin stimulus
GO:0035994
response to muscle stretch
GO:0036092
phosphatidylinositol-3-phosphate biosynthetic process
GO:0038084
vascular endothelial growth factor signaling pathway
GO:0040014
regulation of multicellular organism growth
GO:0043201
response to L-leucine
GO:0043276
anoikis
GO:0043457
regulation of cellular respiration
GO:0043491
phosphatidylinositol 3-kinase/protein kinase B signal transduction
GO:0043524
negative regulation of neuron apoptotic process
GO:0043542
endothelial cell migration
GO:0046854
phosphatidylinositol phosphate biosynthetic process
GO:0048009
insulin-like growth factor receptor signaling pathway
GO:0048015
phosphatidylinositol-mediated signaling
GO:0048661
positive regulation of smooth muscle cell proliferation
GO:0050852
T cell receptor signaling pathway
GO:0051897
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
GO:0055119
relaxation of cardiac muscle
GO:0060048
cardiac muscle contraction
GO:0060612
adipose tissue development
GO:0071333
cellular response to glucose stimulus
GO:0071464
cellular response to hydrostatic pressure
GO:0071548
response to dexamethasone
GO:0086003
cardiac muscle cell contraction
GO:0097009
energy homeostasis
GO:0110053
regulation of actin filament organization
GO:0141068
autosome genomic imprinting
GO:1903544
response to butyrate
GO:1905477
positive regulation of protein localization to membrane
GO:2000270
negative regulation of fibroblast apoptotic process
GO:2000811
negative regulation of anoikis
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
GO:0005944
phosphatidylinositol 3-kinase complex, class IB
GO:0014704
intercalated disc
GO:0030027
lamellipodium
GO:0048471
perinuclear region of cytoplasm
View graph for
Molecular Function
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Biological Process
View graph for
Cellular Component
External links
PDB
RCSB:8tsc
,
PDBe:8tsc
,
PDBj:8tsc
PDBsum
8tsc
PubMed
37916956
UniProt
P42336
|PK3CA_HUMAN Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (Gene Name=PIK3CA)
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