Structure of PDB 4ykn Chain A Binding Site BS01

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 2101 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
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)		R1770 M1772 S1774 K1802 Y1836 I1848 V1851 Q1859 S1919 M1922 I1932 D1933
Binding residue
(residue number reindexed from 1)		R928 M930 S932 K960 Y994 I1006 V1009 Q1017 S1077 M1080 I1090 D1091
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

View graph for
Molecular Function
View graph for
Biological Process
View graph for
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)

[Back to BioLiP]