Structure of PDB 2h8h Chain A Binding Site BS01

Receptor Information
>2h8h Chain A (length=445) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
TFVALYDYESRTETDLSFKKGERLQIVNNTEGDWWLAHSLSTGQTGYIPS
NYVAPSDSIQAEEWYFGKITRRESERLLLNAENPRGTFLVRESETTKGAY
CLSVSDFDNAKGLNVKHYKIRKLDSGGFYITSRTQFNSLQQLVAYYSKHA
DGLCHRLTTVCPTSKPQTQGLAKDAWEIPRESLRLEVKLGQGCFGEVWMG
TWNGTTRVAIKTLKPGTMSPEAFLQEAQVMKKLRHEKLVQLYAVVSEEPI
YIVTEYMSKGSLLDFLKGETGKYLRLPQLVDMAAQIASGMAYVERMNYVH
RDLRAANILVGENLVCKVADFGLARLIEDNEYTARQGAKFPIKWTAPEAA
LYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCP
PECPESLHDLMCQCWRKEPEERPTFEYLQAFLEDYFTSTEPQYQP
Ligand information
Ligand IDH8H
InChIInChI=1S/C27H32ClN5O5/c1-32-6-8-33(9-7-32)10-13-35-19-14-21-24(23(15-19)38-18-4-11-34-12-5-18)27(30-16-29-21)31-25-20(28)2-3-22-26(25)37-17-36-22/h2-3,14-16,18H,4-13,17H2,1H3,(H,29,30,31)
InChIKeyOUKYUETWWIPKQR-UHFFFAOYSA-N
SMILES
SoftwareSMILES
CACTVS 3.385CN1CCN(CCOc2cc(OC3CCOCC3)c4c(Nc5c(Cl)ccc6OCOc56)ncnc4c2)CC1
ACDLabs 10.04Clc2ccc1OCOc1c2Nc6ncnc5c6c(OC3CCOCC3)cc(OCCN4CCN(C)CC4)c5
OpenEye OEToolkits 1.7.6CN1CCN(CC1)CCOc2cc3c(c(c2)OC4CCOCC4)c(ncn3)Nc5c(ccc6c5OCO6)Cl
FormulaC27 H32 Cl N5 O5
NameN-(5-CHLORO-1,3-BENZODIOXOL-4-YL)-7-[2-(4-METHYLPIPERAZIN-1-YL)ETHOXY]-5-(TETRAHYDRO-2H-PYRAN-4-YLOXY)QUINAZOLIN-4-AMINE;
SARACATINIB
ChEMBLCHEMBL217092
DrugBankDB11805
ZINCZINC000024811973
PDB chain2h8h Chain A Residue 534 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB2h8h N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor.
Resolution2.2 Å
Binding residue
(original residue number in PDB)		L273 V281 A293 K295 T338 Y340 M341 S342 G344 L393 D404
Binding residue
(residue number reindexed from 1)		L189 V197 A209 K211 T254 Y256 M257 S258 G260 L309 D320
Annotation score1
Binding affinityMOAD: ic50=2.7nM
PDBbind-CN: -logKd/Ki=8.57,IC50=2.7nM
BindingDB: IC50=2.7nM
Enzymatic activity
Catalytic site (original residue number in PDB) D386 R388 A390 N391 D404 F424
Catalytic site (residue number reindexed from 1) D302 R304 A306 N307 D320 F340
Enzyme Commision number 2.7.10.2: non-specific protein-tyrosine kinase.
Gene Ontology
Molecular Function
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004715 non-membrane spanning protein tyrosine kinase activity
GO:0005080 protein kinase C binding
GO:0005102 signaling receptor binding
GO:0005158 insulin receptor binding
GO:0005178 integrin binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016004 phospholipase activator activity
GO:0016301 kinase activity
GO:0019899 enzyme binding
GO:0019901 protein kinase binding
GO:0019904 protein domain specific binding
GO:0020037 heme binding
GO:0030331 nuclear estrogen receptor binding
GO:0042169 SH2 domain binding
GO:0043274 phospholipase binding
GO:0044325 transmembrane transporter binding
GO:0044877 protein-containing complex binding
GO:0045296 cadherin binding
GO:0046875 ephrin receptor binding
GO:0050839 cell adhesion molecule binding
GO:0051117 ATPase binding
GO:0051219 phosphoprotein binding
GO:0070700 BMP receptor binding
GO:0071253 connexin binding
GO:0097110 scaffold protein binding
Biological Process
GO:0000122 negative regulation of transcription by RNA polymerase II
GO:0001545 primary ovarian follicle growth
GO:0001819 positive regulation of cytokine production
GO:0002223 stimulatory C-type lectin receptor signaling pathway
GO:0002376 immune system process
GO:0002862 negative regulation of inflammatory response to antigenic stimulus
GO:0006468 protein phosphorylation
GO:0007155 cell adhesion
GO:0007165 signal transduction
GO:0007172 signal complex assembly
GO:0007173 epidermal growth factor receptor signaling pathway
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007229 integrin-mediated signaling pathway
GO:0007283 spermatogenesis
GO:0007611 learning or memory
GO:0008284 positive regulation of cell population proliferation
GO:0009410 response to xenobiotic stimulus
GO:0009612 response to mechanical stimulus
GO:0010447 response to acidic pH
GO:0010628 positive regulation of gene expression
GO:0010629 negative regulation of gene expression
GO:0010632 regulation of epithelial cell migration
GO:0010634 positive regulation of epithelial cell migration
GO:0010907 positive regulation of glucose metabolic process
GO:0010954 positive regulation of protein processing
GO:0014856 skeletal muscle cell proliferation
GO:0014911 positive regulation of smooth muscle cell migration
GO:0016236 macroautophagy
GO:0016310 phosphorylation
GO:0016477 cell migration
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0022407 regulation of cell-cell adhesion
GO:0030154 cell differentiation
GO:0030168 platelet activation
GO:0030900 forebrain development
GO:0031295 T cell costimulation
GO:0031333 negative regulation of protein-containing complex assembly
GO:0031648 protein destabilization
GO:0031667 response to nutrient levels
GO:0032205 negative regulation of telomere maintenance
GO:0032869 cellular response to insulin stimulus
GO:0033146 regulation of intracellular estrogen receptor signaling pathway
GO:0033625 positive regulation of integrin activation
GO:0034139 regulation of toll-like receptor 3 signaling pathway
GO:0034332 adherens junction organization
GO:0034446 substrate adhesion-dependent cell spreading
GO:0034614 cellular response to reactive oxygen species
GO:0035306 positive regulation of dephosphorylation
GO:0035331 negative regulation of hippo signaling
GO:0035556 intracellular signal transduction
GO:0036035 osteoclast development
GO:0036120 cellular response to platelet-derived growth factor stimulus
GO:0038083 peptidyl-tyrosine autophosphorylation
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0038128 ERBB2 signaling pathway
GO:0038166 angiotensin-activated signaling pathway
GO:0042476 odontogenesis
GO:0042542 response to hydrogen peroxide
GO:0043065 positive regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043114 regulation of vascular permeability
GO:0043149 stress fiber assembly
GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0045056 transcytosis
GO:0045087 innate immune response
GO:0045124 regulation of bone resorption
GO:0045453 bone resorption
GO:0045747 positive regulation of Notch signaling pathway
GO:0045780 positive regulation of bone resorption
GO:0045785 positive regulation of cell adhesion
GO:0045821 positive regulation of glycolytic process
GO:0046579 positive regulation of Ras protein signal transduction
GO:0046628 positive regulation of insulin receptor signaling pathway
GO:0046718 symbiont entry into host cell
GO:0046777 protein autophosphorylation
GO:0048008 platelet-derived growth factor receptor signaling pathway
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0048011 neurotrophin TRK receptor signaling pathway
GO:0048013 ephrin receptor signaling pathway
GO:0048041 focal adhesion assembly
GO:0048477 oogenesis
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050847 progesterone receptor signaling pathway
GO:0050900 leukocyte migration
GO:0051057 positive regulation of small GTPase mediated signal transduction
GO:0051222 positive regulation of protein transport
GO:0051385 response to mineralocorticoid
GO:0051450 myoblast proliferation
GO:0051602 response to electrical stimulus
GO:0051895 negative regulation of focal adhesion assembly
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
GO:0051902 negative regulation of mitochondrial depolarization
GO:0060065 uterus development
GO:0060444 branching involved in mammary gland duct morphogenesis
GO:0060491 regulation of cell projection assembly
GO:0060576 intestinal epithelial cell development
GO:0070102 interleukin-6-mediated signaling pathway
GO:0070301 cellular response to hydrogen peroxide
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0070542 response to fatty acid
GO:0070555 response to interleukin-1
GO:0071222 cellular response to lipopolysaccharide
GO:0071375 cellular response to peptide hormone stimulus
GO:0071393 cellular response to progesterone stimulus
GO:0071398 cellular response to fatty acid
GO:0071456 cellular response to hypoxia
GO:0071498 cellular response to fluid shear stress
GO:0071560 cellular response to transforming growth factor beta stimulus
GO:0071803 positive regulation of podosome assembly
GO:0071897 DNA biosynthetic process
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0086091 regulation of heart rate by cardiac conduction
GO:0090263 positive regulation of canonical Wnt signaling pathway
GO:0098609 cell-cell adhesion
GO:1900182 positive regulation of protein localization to nucleus
GO:1902533 positive regulation of intracellular signal transduction
GO:1903997 positive regulation of non-membrane spanning protein tyrosine kinase activity
GO:1904263 positive regulation of TORC1 signaling
GO:1904385 cellular response to angiotensin
GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation
GO:1990646 cellular response to prolactin
GO:2000256 positive regulation of male germ cell proliferation
GO:2000386 positive regulation of ovarian follicle development
GO:2000394 positive regulation of lamellipodium morphogenesis
GO:2000588 positive regulation of platelet-derived growth factor receptor-beta signaling pathway
GO:2000641 regulation of early endosome to late endosome transport
GO:2000811 negative regulation of anoikis
GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
GO:2001286 regulation of caveolin-mediated endocytosis
Cellular Component
GO:0002102 podosome
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005743 mitochondrial inner membrane
GO:0005764 lysosome
GO:0005770 late endosome
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005884 actin filament
GO:0005886 plasma membrane
GO:0005901 caveola
GO:0005925 focal adhesion
GO:0016020 membrane
GO:0030054 cell junction
GO:0032587 ruffle membrane
GO:0043025 neuronal cell body
GO:0044294 dendritic growth cone
GO:0045121 membrane raft
GO:0048471 perinuclear region of cytoplasm
GO:0070062 extracellular exosome
GO:0070161 anchoring junction
GO:0097060 synaptic membrane
GO:0098978 glutamatergic synapse
GO:0099091 postsynaptic specialization, intracellular component
GO:1902737 dendritic filopodium

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:2h8h, PDBe:2h8h, PDBj:2h8h
PDBsum2h8h
PubMed17064066
UniProtP12931|SRC_HUMAN Proto-oncogene tyrosine-protein kinase Src (Gene Name=SRC)

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