Structure of PDB 5ukj Chain A Binding Site BS01

Receptor Information
>5ukj Chain A (length=1009) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
PPRPSSGELWGIHLMPPRILVECLLPNGMIVTLECLREATLITIKHELFK
EARKYPLHQLLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKV
IEPVGNREEKILNREIGFAIGMPVCEFDMVKDPEVQDFRRNILNVCKEAV
DLRDLNSPHSRAMYVYPPNVESSPELPKHIYNKLDKGQIIVVIWVIVSPN
NDKQKYTLKINHDCVPEQVIAEAIRKKEQLKLCVLEYQGKYILKVCGCDE
YFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKESLYSQLPMDCFTMPSYSR
RISTSTKSLWVINSALRIKILCATYVNVNIRDIDKIYVRTGIYHGGEPLC
DNVNTQRVPCSNPRWNEWLNYDIYIPDLPRAARLCLSICSVKGRKGAKEE
HCPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNK
ETPCLELEFDWFSSVVKFPDMSVIEEHANWSVSRELRENDKEQLKAISTR
DPLSEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLV
KDWPPIKPEQAMELLDCNYPDPMVRGFAVRCLEKYLTDDKLSQYLIQLVQ
VLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNKTVSQRFGLL
LESYCRACGMYLKHLNRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVE
QMRRPDFMDALQGFLSPLNPAHQLGNLRLEECEIMSSAKRPLKLNWENPD
IMSELLFQNNIIMFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYG
CLSIGDCVGLIEWVRNSHTIMQIQCKQFNSHTLHQWLKDKNKGEIYDAAI
DLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLVHIDFGHFLDHKKKK
FGYKRERVPFVLTQDFLIVISKGAQECTKTREFERFQEMCYKAYLAIRQH
ANLFINLFSMMLGSGMPELQSFDDIAYIRKTLALDKTEQEALEYFMKQMN
DAHHGGWTT
Ligand information
Ligand ID3K6
InChIInChI=1S/C22H24N6O2S/c1-15-13-28-21(14-27(15)20-9-11-24-22-18(20)8-10-23-22)19(12-25-28)16-4-6-17(7-5-16)31(29,30)26(2)3/h4-12,15H,13-14H2,1-3H3,(H,23,24)/t15-/m1/s1
InChIKeyUGAYOLUDSWRLMK-OAHLLOKOSA-N
SMILES
SoftwareSMILES
CACTVS 3.385C[CH]1Cn2ncc(c2CN1c3ccnc4[nH]ccc34)c5ccc(cc5)[S](=O)(=O)N(C)C
CACTVS 3.385C[C@@H]1Cn2ncc(c2CN1c3ccnc4[nH]ccc34)c5ccc(cc5)[S](=O)(=O)N(C)C
OpenEye OEToolkits 1.9.2CC1Cn2c(c(cn2)c3ccc(cc3)S(=O)(=O)N(C)C)CN1c4ccnc5c4cc[nH]5
OpenEye OEToolkits 1.9.2C[C@@H]1Cn2c(c(cn2)c3ccc(cc3)S(=O)(=O)N(C)C)CN1c4ccnc5c4cc[nH]5
ACDLabs 12.01O=S(=O)(N(C)C)c5ccc(c1c4n(nc1)CC(N(c3ccnc2nccc23)C4)C)cc5
FormulaC22 H24 N6 O2 S
NameN,N-dimethyl-4-[(6R)-6-methyl-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl]benzenesulfonamide
ChEMBLCHEMBL3355071
DrugBank
ZINCZINC000221478513
PDB chain5ukj 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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PDB5ukj Rationally Designed PI3K alpha Mutants to Mimic ATR and Their Use to Understand Binding Specificity of ATR Inhibitors.
Resolution2.8 Å
Binding residue
(original residue number in PDB)		M800 K802 I848 E849 W850 V851 S854 Q859 M922 I932 D933
Binding residue
(residue number reindexed from 1)		M763 K765 I811 E812 W813 V814 S817 Q822 M878 I888 D889
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=7.16,Kd=0.069uM
BindingDB: IC50=>10000nM
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

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:5ukj, PDBe:5ukj, PDBj:5ukj
PDBsum5ukj
PubMed28433539
UniProtP42336|PK3CA_HUMAN Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (Gene Name=PIK3CA)

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