Structure of PDB 4fc0 Chain A Binding Site BS01

Receptor Information
>4fc0 Chain A (length=254) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
DDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDVAVKMLNVTAPTPQQLQA
FKNEVGVLRKTRHVNILLFMGYSTKPQLAIVTQWCEGSSLYHHLHIIETK
FEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGG
SILWMAPEVIRMNPYSFQSDVYAFGIVLYELMTGQLPYSNINNRDQIIFM
VGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDERPLFPQILASIELLA
RSLP
Ligand information
Ligand ID0T2
InChIInChI=1S/C28H24ClFN6O3S/c1-28(2,14-31)39-21-6-4-5-17(23(21)29)25(38)32-20-13-16(9-10-18(20)30)36(3)22-12-11-19-26(34-22)40-27(33-19)35-24(37)15-7-8-15/h4-6,9-13,15H,7-8H2,1-3H3,(H,32,38)(H,33,35,37)
InChIKeyBSBQPLUISHJULY-UHFFFAOYSA-N
SMILES
SoftwareSMILES
ACDLabs 12.01N#CC(Oc1cccc(c1Cl)C(=O)Nc2c(F)ccc(c2)N(c3nc4sc(nc4cc3)NC(=O)C5CC5)C)(C)C
CACTVS 3.370CN(c1ccc(F)c(NC(=O)c2cccc(OC(C)(C)C#N)c2Cl)c1)c3ccc4nc(NC(=O)C5CC5)sc4n3
OpenEye OEToolkits 1.7.6CC(C)(C#N)Oc1cccc(c1Cl)C(=O)Nc2cc(ccc2F)N(C)c3ccc4c(n3)sc(n4)NC(=O)C5CC5
FormulaC28 H24 Cl F N6 O3 S
Name2-chloro-3-[(2-cyanopropan-2-yl)oxy]-N-{5-[{2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}(methyl)amino]-2-fluorophenyl}benzamide
ChEMBLCHEMBL2204532
DrugBank
ZINCZINC000059083698
PDB chain4fc0 Chain A Residue 901 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4fc0 Design and synthesis of novel DFG-out RAF/vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors: 3. Evaluation of 5-amino-linked thiazolo[5,4-d]pyrimidine and thiazolo[5,4-b]pyridine derivatives.
Resolution2.95 Å
Binding residue
(original residue number in PDB)		A480 K482 E500 V503 L504 L513 I526 T528 W530 C531 G533 G592 D593 F594
Binding residue
(residue number reindexed from 1)		A34 K36 E54 V57 L58 L67 I80 T82 W84 C85 G87 G146 D147 F148
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=7.16,IC50=69nM
BindingDB: IC50=69nM
Enzymatic activity
Catalytic site (original residue number in PDB) D575 K577 N579 N580 D593 S615
Catalytic site (residue number reindexed from 1) D129 K131 N133 N134 D147 S151
Enzyme Commision number 2.7.11.1: non-specific serine/threonine protein kinase.
Gene Ontology
Molecular Function
GO:0004672 protein kinase activity
GO:0005524 ATP binding
Biological Process
GO:0006468 protein phosphorylation

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Molecular Function
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Biological Process
External links
PDB RCSB:4fc0, PDBe:4fc0, PDBj:4fc0
PDBsum4fc0
PubMed22883026
UniProtP15056|BRAF_HUMAN Serine/threonine-protein kinase B-raf (Gene Name=BRAF)

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