Structure of PDB 4zop Chain A Binding Site BS01

Receptor Information

>4zop Chain A (length=1000) 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
NDKQKYTLKINHDCVPEQVIAEAIRKKYQGKYILKVCGCDEYFLEKYPLS
QYKYIRSCIMLGRMPNLMLMAKESLYSQLPMDCFTMPSYSRRISTASTKS
LWVINSALRIKILCATYVNVNIRDIDKIYVRTGIYHGGEPLCDNVNTQRV
PCSNPRWNEWLNYDIYIPDLPRAARLCLSICSVKGRKGAKEEHCPLAWGN
INLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKETPCLELE
FDWFSSVVKFPDMSVIEEHAENDKEQLKAISTRDPLSEITEQEKDFLWSH
RHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAMELLDC
NYPDPMVRGFAVRCLEKYLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLL
KKALTNQRIGHFFFWHLKSEMHNKTVSQRFGLLLESYCRACGMYLKHLNR
QVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSP
LNPAHQLGNLRLEECRIMSSAKRPLWLNWENPDIMSELLFQNNEIIFKNG
DDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNS
HTIMQIQCKGFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFIL
GIGDRHNSNIMVKDDGQLFHIDFGHFLDHKKKKFGYKRERVPFVLTQDFL
IVISKGAQECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMP
ELQSFDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHT

Ligand information

Ligand ID

4Q2

InChI

InChI=1S/C20H26N6O2S/c1-10-7-8-26(14(10)16(21)27)19(28)25-18-23-12-6-5-11-9-22-17(20(2,3)4)24-13(11)15(12)29-18/h9-10,14H,5-8H2,1-4H3,(H2,21,27)(H,23,25,28)/t10-,14+/m1/s1

InChIKey

NUGMMEMSYIUTGA-YGRLFVJLSA-N

SMILES

Software	SMILES
ACDLabs 12.01	C2Cc1nc(sc1c3c2cnc(n3)C(C)(C)C)NC(N4C(C(C)CC4)C(N)=O)=O
OpenEye OEToolkits 1.9.2	CC1CCN(C1C(=O)N)C(=O)Nc2nc3c(s2)-c4c(cnc(n4)C(C)(C)C)CC3
CACTVS 3.385	C[C@@H]1CCN([C@@H]1C(N)=O)C(=O)Nc2sc3c(CCc4cnc(nc34)C(C)(C)C)n2
OpenEye OEToolkits 1.9.2	C[C@@H]1CCN([C@@H]1C(=O)N)C(=O)Nc2nc3c(s2)-c4c(cnc(n4)C(C)(C)C)CC3
CACTVS 3.385	C[CH]1CCN([CH]1C(N)=O)C(=O)Nc2sc3c(CCc4cnc(nc34)C(C)(C)C)n2

Formula

C20 H26 N6 O2 S

Name

(2S,3R)-N~1~-(8-tert-butyl-4,5-dihydro[1,3]thiazolo[4,5-h]quinazolin-2-yl)-3-methylpyrrolidine-1,2-dicarboxamide

PDB chain

4zop Chain A Residue 1101 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]

Receptor-Ligand Complex Structure

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Structure summary

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PDB	4zop Co-crystal Structure of the Lipid Kinase PI3K alpha with a selective phosphatidylinositol-3 kinase alpha inhibitorCo-crystal Structure of the Lipid Kinase PI3K alpha with a selective phosphatidylinositol-3 kinase alpha inhibitor
Resolution	2.62 Å
Binding residue (original residue number in PDB)	W780 Y836 I848 E849 V851 S854 H855 Q859 I932
Binding residue (residue number reindexed from 1)	W726 Y782 I794 E795 V797 S800 H801 Q805 I871
Annotation score	1
Binding affinity	BindingDB: IC50=6.0nM

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:4zop, PDBe:4zop, PDBj:4zop
PDBsum	4zop
PubMed
UniProt	P42336\|PK3CA_HUMAN Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (Gene Name=PIK3CA)

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