Structure of PDB 4u0i Chain A Binding Site BS01

Receptor Information
>4u0i 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]
GNNYVYIDPTQLPYDHKWEFPRNRLSFGKTLGAGAFGKVVEATAYGLIAA
MTVAVKMLKPSAHLTEREALMSELKVLSYLGNHMNIVNLLGACTIGGPTL
VITEYCCYGDLLNFLRRKRDSFICSLALDLEDLLSFSYQVAKGMAFLASK
NCIHRDLAARNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWM
APESIFNCVYTFESDVWSYGIFLWELFSLGSSPYPGMPVDSKFYKMIKEG
FRMLSPEHAPAEMYDIMKTCWDADPLKRPTFKQIVQLIEKQISESTN
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 chain4u0i Chain A Residue 1001 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4u0i Ponatinib Inhibits Polyclonal Drug-Resistant KIT Oncoproteins and Shows Therapeutic Potential in Heavily Pretreated Gastrointestinal Stromal Tumor (GIST) Patients.
Resolution2.0 Å
Binding residue
(original residue number in PDB)		L595 A621 V622 K623 E640 T670 Y672 C673 I789 H790 R791 L799 C809 D810 F811
Binding residue
(residue number reindexed from 1)		L31 A54 V55 K56 E73 T103 Y105 C106 I153 H154 R155 L163 C173 D174 F175
Annotation score1
Binding affinityMOAD: ic50<11nM
PDBbind-CN: -logKd/Ki=8.22,IC50=6nM
BindingDB: IC50=1.7nM
Enzymatic activity
Catalytic site (original residue number in PDB) D792 R796 N797 D810
Catalytic site (residue number reindexed from 1) D156 R160 N161 D174
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:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0005524 ATP binding
Biological Process
GO:0006468 protein phosphorylation
GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway

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Molecular Function
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Biological Process
External links
PDB RCSB:4u0i, PDBe:4u0i, PDBj:4u0i
PDBsum4u0i
PubMed25239608
UniProtP10721|KIT_HUMAN Mast/stem cell growth factor receptor Kit (Gene Name=KIT)

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