Structure of PDB 4ykn Chain A Binding Site BS02

Receptor Information
>4ykn Chain A (length=1205) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
AEWYWGDISREEVNEKLRDTADGTFLVRDYTLTLRKGGNNKLIKIFHYGF
SDPLTVVELINHYRNKLDVKLLYPVYNTQFQEKSREYDRLYEEYTRTSQE
IQMKRTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEKEIQRIMH
NYDKLKSRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKT
RDQYLWGIHLMPPRILVECLLPNGMIVTLECLREATLITIKHELFKEARK
YPLHQLLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEPV
GNREEKILNREIGFAIGMPVCEFDMVKDPEVQDFRRNILNVCKEAVDLRD
LNSPHSRAMYVYPPNVESSPELPKHIYNKLDKGQIIVVIWVIVSPNNDKQ
KYTLKINHDCVPEQVIAEAIRKKTRSMLLSSEQLKLCVLEYQGKYILKVC
GCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKESLYSQLPMDCFTMP
SYSRSTKSLWVINSALRIKILCATYVNVNIIDKIYVRTGIYHGGEPLCDN
VNTQRVPCSNPRWNEWLNYDIYIPDLPRAARLCLSICSVKGAKEEHCPLA
WGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKETPCL
ELEFDWFSSVVKFPDMSVIEEHANWSVSRELRENDKEQLKAISTRDPLSE
ITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPP
IKPEQAMELLDCNYPDPMVRGFAVRCLEKYLTDDKLSQYLIQLVQVLKYE
QYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNKTVSQRFGLLLESYC
RACGMYLKHLNRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRP
DFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLWLNWENPDIMSEL
LFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIG
DCVGLIEVVRNSHTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDA
AIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLDHKK
KKERVPFVLTQDFLIVISKGAQECTKTREFERFQEMCYKAYLAIRQHANL
FINLFSMMLGSGMPELQSFDDIAYIRKTLALDKTEQEALEYFMKQMNDAH
HGGWT
Ligand information
Ligand ID4EL
InChIInChI=1S/C23H21N5O5S2/c1-14-26-27-23(34-14)28-35(31,32)20-6-4-19(5-7-20)24-12-15-9-17(11-18(10-15)22(29)30)16-3-8-21(33-2)25-13-16/h3-11,13,24H,12H2,1-2H3,(H,27,28)(H,29,30)
InChIKeyCBZPCOUPBNLTKW-UHFFFAOYSA-N
SMILES
SoftwareSMILES
ACDLabs 12.01c2c(c1ccc(OC)nc1)cc(cc2CNc4ccc(S(=O)(Nc3nnc(C)s3)=O)cc4)C(O)=O
OpenEye OEToolkits 1.9.2Cc1nnc(s1)NS(=O)(=O)c2ccc(cc2)NCc3cc(cc(c3)C(=O)O)c4ccc(nc4)OC
CACTVS 3.385COc1ccc(cn1)c2cc(CNc3ccc(cc3)[S](=O)(=O)Nc4sc(C)nn4)cc(c2)C(O)=O
FormulaC23 H21 N5 O5 S2
Name3-(6-methoxypyridin-3-yl)-5-[({4-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfamoyl]phenyl}amino)methyl]benzoic acid
ChEMBLCHEMBL3582354
DrugBank
ZINCZINC000230585752
PDB chain4ykn Chain A Residue 2102 [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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PDB4ykn Discovery of a Potent Class of PI3K alpha Inhibitors with Unique Binding Mode via Encoded Library Technology (ELT).
Resolution2.9 Å
Binding residue
(original residue number in PDB)		W1328 V1329 H1495 R1577
Binding residue
(residue number reindexed from 1)		W510 V511 H672 R735
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=8.00,IC50=10nM
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:4ykn, PDBe:4ykn, PDBj:4ykn
PDBsum4ykn
PubMed26005528
UniProtP27986|P85A_HUMAN Phosphatidylinositol 3-kinase regulatory subunit alpha (Gene Name=PIK3R1);
P42336|PK3CA_HUMAN Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (Gene Name=PIK3CA)

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