Structure of PDB 5hg7 Chain A Binding Site BS01

Receptor Information
>5hg7 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]
ALLRILKETEFKKIKVLGSGAFGTVYKGLWIPEGEKVKIPVAIKELRSPK
ANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLIMQLMPFGCLLDYVRE
HKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKIT
DFGRAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTV
WELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMRKCWMID
ADSRPKFRELIIEFSKMARDPQRYLVIQGD
Ligand information
Ligand ID630
InChIInChI=1S/C19H24ClN7O3/c1-4-15(28)27-7-11(14(9-27)29-3)10-30-18-16-13(20)6-21-17(16)24-19(25-18)23-12-5-22-26(2)8-12/h5-6,8,11,14H,4,7,9-10H2,1-3H3,(H2,21,23,24,25)/t11-,14+/m1/s1
InChIKeyLYWNQEMCSWYHEM-RISCZKNCSA-N
SMILES
SoftwareSMILES
CACTVS 3.385CCC(=O)N1C[C@H](COc2nc(Nc3cnn(C)c3)nc4[nH]cc(Cl)c24)[C@H](C1)OC
CACTVS 3.385CCC(=O)N1C[CH](COc2nc(Nc3cnn(C)c3)nc4[nH]cc(Cl)c24)[CH](C1)OC
OpenEye OEToolkits 2.0.4CCC(=O)N1CC(C(C1)OC)COc2c3c(c[nH]c3nc(n2)Nc4cnn(c4)C)Cl
ACDLabs 12.01N(c1cn(nc1)C)c3nc(OCC2C(CN(C(CC)=O)C2)OC)c4c(n3)ncc4Cl
OpenEye OEToolkits 2.0.4CCC(=O)N1C[C@@H]([C@H](C1)OC)COc2c3c(c[nH]c3nc(n2)Nc4cnn(c4)C)Cl
FormulaC19 H24 Cl N7 O3
Name1-{(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}propan-1-one;
Bound form of PF-06459988;
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
ChEMBL
DrugBank
ZINCZINC000263620727
PDB chain5hg7 Chain A Residue 9001 [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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PDB5hg7 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.
Resolution1.85 Å
Binding residue
(original residue number in PDB)		L718 F723 V726 A743 C775 M790 Q791 M793 P794 G796 C797 R841 L844 F856
Binding residue
(residue number reindexed from 1)		L17 F22 V25 A42 C71 M86 Q87 M89 P90 G92 C93 R137 L140 F152
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=8.40,Ki=4nM
Enzymatic activity
Catalytic site (original residue number in PDB) D837 A839 R841 N842 D855 G874
Catalytic site (residue number reindexed from 1) D133 A135 R137 N138 D151 G170
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:5hg7, PDBe:5hg7, PDBj:5hg7
PDBsum5hg7
PubMed26756222
UniProtP00533|EGFR_HUMAN Epidermal growth factor receptor (Gene Name=EGFR)

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