Structure of PDB 5hg9 Chain A Binding Site BS01

Receptor Information
>5hg9 Chain A (length=280) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
ALLRILKETEFKKIKVLGSGAFGTVYKGLWIPEGEKVKIPVAIKELRPKA
NKEILDEAYVMASVDNPHVCRLLGICLTSTVQLIMQLMPFGCLLDYVREH
KDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITD
FGRAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVW
ELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMRKCWMIDA
DSRPKFRELIIEFSKMARDPQRYLVIQGDE
Ligand information
Ligand ID63A
InChIInChI=1S/C19H22F3N7O2/c1-3-15(30)29-7-11(14(9-29)19(20,21)22)10-31-17-13-4-5-23-16(13)26-18(27-17)25-12-6-24-28(2)8-12/h4-6,8,11,14H,3,7,9-10H2,1-2H3,(H2,23,25,26,27)/t11-,14+/m1/s1
InChIKeyCKVDMJWQTVJZKC-RISCZKNCSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 2.0.4CCC(=O)N1CC(C(C1)C(F)(F)F)COc2c3cc[nH]c3nc(n2)Nc4cnn(c4)C
CACTVS 3.385CCC(=O)N1C[C@H](COc2nc(Nc3cnn(C)c3)nc4[nH]ccc24)[C@H](C1)C(F)(F)F
CACTVS 3.385CCC(=O)N1C[CH](COc2nc(Nc3cnn(C)c3)nc4[nH]ccc24)[CH](C1)C(F)(F)F
ACDLabs 12.01N1(C(=O)CC)CC(C(F)(F)F)C(C1)COc2c4c(nc(n2)Nc3cn(nc3)C)ncc4
OpenEye OEToolkits 2.0.4CCC(=O)N1C[C@@H]([C@H](C1)C(F)(F)F)COc2c3cc[nH]c3nc(n2)Nc4cnn(c4)C
FormulaC19 H22 F3 N7 O2
Name1-[(3R,4R)-3-[({2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)methyl]-4-(trifluoromethyl)pyrr olidin-1-yl]propan-1-one;
Bound form of 1-[(3R,4R)-3-[({2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)methyl]-4-(trifluoromethyl)pyrro lidin-1-yl]prop-2-en-1-one
ChEMBL
DrugBank
ZINCZINC000263620314
PDB chain5hg9 Chain A Residue 9001 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB5hg9 Discovery of 1-{(3R,4R)-3-[({5-Chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)methyl]-4-methoxypyrrolidin-1-yl}prop-2-en-1-one (PF-06459988), a Potent, WT Sparing, Irreversible Inhibitor of T790M-Containing EGFR Mutants.
Resolution2.15 Å
Binding residue
(original residue number in PDB)		L718 G719 S720 F723 V726 A743 M793 G796 C797 R841 L844
Binding residue
(residue number reindexed from 1)		L17 G18 S19 F22 V25 A42 M88 G91 C92 R136 L139
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=7.46,Ki=35nM
Enzymatic activity
Catalytic site (original residue number in PDB) D837 A839 R841 N842 D855 G874
Catalytic site (residue number reindexed from 1) D132 A134 R136 N137 D150 G169
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:5hg9, PDBe:5hg9, PDBj:5hg9
PDBsum5hg9
PubMed26756222
UniProtP00533|EGFR_HUMAN Epidermal growth factor receptor (Gene Name=EGFR)

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