Structure of PDB 6eg9 Chain B Binding Site BS01

Receptor Information
>6eg9 Chain B (length=274) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
FHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKK
LAAITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPN
GSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANI
LLDEAFTAKISDFVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLP
AVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQ
CLHEKKNKRPDIKKVQQLLQEMTA
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 chain6eg9 Chain B Residue 501 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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PDB6eg9 Conformational flexibility and inhibitor binding to unphosphorylated interleukin-1 receptor-associated kinase 4 (IRAK4).
Resolution2.414 Å
Binding residue
(original residue number in PDB)		M192 A211 K213 E233 M237 V246 Y262 Y264 M265 I308 H309 L318 S328 D329 F330
Binding residue
(residue number reindexed from 1)		M28 A47 K49 E66 M70 V79 Y95 Y97 M98 I141 H142 L151 S161 D162 F163
Annotation score1
Binding affinityMOAD: ic50=66.9nM
Enzymatic activity
Catalytic site (original residue number in PDB) D311 K313 A315 N316 D329 T351
Catalytic site (residue number reindexed from 1) D144 K146 A148 N149 D162 T166
Enzyme Commision number 2.7.11.1: non-specific serine/threonine protein kinase.
Gene Ontology
Molecular Function
GO:0000287 magnesium ion binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0005524 ATP binding
Biological Process
GO:0006468 protein phosphorylation
GO:0007165 signal transduction

View graph for
Molecular Function
View graph for
Biological Process
External links
PDB RCSB:6eg9, PDBe:6eg9, PDBj:6eg9
PDBsum6eg9
PubMed30679311
UniProtQ9NWZ3|IRAK4_HUMAN Interleukin-1 receptor-associated kinase 4 (Gene Name=IRAK4)

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