Structure of PDB 4uxq Chain A Binding Site BS01

Receptor Information
>4uxq Chain A (length=286) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
LDLPLDPLWEFPRDRLVLGKPLGEGAFGQVVRAEAFGMDPARPDQASTVA
VKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVCTQEGPLYVIVE
CAAKGNLREFLRARRPPGPLSFPVLVSCAYQVARGMQYLESRKCIHRDLA
ARNVLVTEDNVMKIADFGLARGVHHIDYYKKTSNGRLPVKWMAPEALFDR
VYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGHRMDRPPHC
PPELYGLMRECWHAAPSQRPTFKQLVEALDKVLLAV
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 chain4uxq Chain A Residue 1752 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4uxq Structural Insights Into Fgfr Kinase Isoform Selectivity: Diverse Binding Modes of Azd4547 and Ponatinib in Complex with Fgfr1 and Fgfr4
Resolution1.85 Å
Binding residue
(original residue number in PDB)		L473 V481 A501 K503 E520 M524 I527 I534 V550 A553 I609 H610 R611 L619 I628 A629 D630 F631
Binding residue
(residue number reindexed from 1)		L22 V30 A50 K52 E69 M73 I76 I83 V99 A102 I145 H146 R147 L155 I164 A165 D166 F167
Annotation score1
Binding affinityMOAD: Kd=16nM
PDBbind-CN: -logKd/Ki=7.80,Kd=16.0nM
BindingDB: IC50=8.0nM
Enzymatic activity
Catalytic site (original residue number in PDB) D612 A614 R616 N617 D630 D641 R650
Catalytic site (residue number reindexed from 1) D148 A150 R152 N153 D166 D177 R186
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:4uxq, PDBe:4uxq, PDBj:4uxq
PDBsum4uxq
PubMed25465127
UniProtP22455|FGFR4_HUMAN Fibroblast growth factor receptor 4 (Gene Name=FGFR4)

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