Structure of PDB 4qrc Chain A Binding Site BS01

Receptor Information
>4qrc Chain A (length=297) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
LPLDPLWEFPRDRLVLGKPLGEGAFGQVVRAEAFGMDPARPDQASTVAVK
MLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVCTQEGPLYVIVECA
AKGNLREFLRARRPPGPDLSPDGPRSSEGPLSFPVLVSCAYQVARGMQYL
ESRKCIHRDLAARNVLVTEDNVMKIADFGLARGVHHIDYYKKTSNGRLPV
KWMAPEALFDEVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLR
EGHRMDRPPHCPPELYGLMRECWHAAPSQRPTFKQLVEALDKVLLAV
Ligand information
Ligand ID0LI
InChIInChI=1S/C29H27F3N6O/c1-20-5-6-22(16-21(20)8-10-25-18-33-27-4-3-11-34-38(25)27)28(39)35-24-9-7-23(26(17-24)29(30,31)32)19-37-14-12-36(2)13-15-37/h3-7,9,11,16-18H,12-15,19H2,1-2H3,(H,35,39)
InChIKeyPHXJVRSECIGDHY-UHFFFAOYSA-N
SMILES
SoftwareSMILES
CACTVS 3.370CN1CCN(CC1)Cc2ccc(NC(=O)c3ccc(C)c(c3)C#Cc4cnc5cccnn45)cc2C(F)(F)F
ACDLabs 12.01FC(F)(F)c1cc(ccc1CN2CCN(C)CC2)NC(=O)c5cc(C#Cc3cnc4cccnn34)c(cc5)C
OpenEye OEToolkits 1.7.6Cc1ccc(cc1C#Cc2cnc3n2nccc3)C(=O)Nc4ccc(c(c4)C(F)(F)F)CN5CCN(CC5)C
FormulaC29 H27 F3 N6 O
Name3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzam ide;
Ponatinib
ChEMBLCHEMBL1171837
DrugBankDB08901
ZINCZINC000036701290
PDB chain4qrc Chain A Residue 802 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4qrc DFG-out Mode of Inhibition by an Irreversible Type-1 Inhibitor Capable of Overcoming Gate-Keeper Mutations in FGF Receptors.
Resolution1.901 Å
Binding residue
(original residue number in PDB)		L473 A501 K503 E520 M524 V550 C552 A553 L603 C608 I609 H610 R611 L619 A629 D630 F631 L633
Binding residue
(residue number reindexed from 1)		L20 A48 K50 E67 M71 V97 C99 A100 L150 C155 I156 H157 R158 L166 A176 D177 F178 L180
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=6.34,IC50=452nM
BindingDB: IC50=8.0nM
Enzymatic activity
Catalytic site (original residue number in PDB) D612 A614 R616 N617 D630 R650
Catalytic site (residue number reindexed from 1) D159 A161 R163 N164 D177 R197
Enzyme Commision number 2.7.10.1: receptor protein-tyrosine kinase.
Gene Ontology
Molecular Function
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine 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:4qrc, PDBe:4qrc, PDBj:4qrc
PDBsum4qrc
PubMed25317566
UniProtP22455|FGFR4_HUMAN Fibroblast growth factor receptor 4 (Gene Name=FGFR4)

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