Structure of PDB 5kz0 Chain A Binding Site BS01

Receptor Information
>5kz0 Chain A (length=293) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
NPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVPLQVAVK
TLPEVCSEQDELDFLMEALIISKFNHQNIVRCIGVSLQSLPRFILLELMA
GGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDI
AARNCLLTCPGPGRVAKIGDFGMARDIGGCAMLPVKWMPPEAFMEGIFTS
KTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPV
YRIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEY
Ligand information
Ligand ID6YL
InChIInChI=1S/C21H24FN5O2/c1-12-18(11-27(5)25-12)14-8-19(20(23)24-10-14)29-13(2)17-9-15(22)6-7-16(17)21(28)26(3)4/h6-11,13H,1-5H3,(H2,23,24)/t13-/m1/s1
InChIKeyCZKOZZRYDBLSRF-CYBMUJFWSA-N
SMILES
SoftwareSMILES
CACTVS 3.385C[CH](Oc1cc(cnc1N)c2cn(C)nc2C)c3cc(F)ccc3C(=O)N(C)C
CACTVS 3.385C[C@@H](Oc1cc(cnc1N)c2cn(C)nc2C)c3cc(F)ccc3C(=O)N(C)C
OpenEye OEToolkits 2.0.5Cc1c(cn(n1)C)c2cc(c(nc2)N)O[C@H](C)c3cc(ccc3C(=O)N(C)C)F
OpenEye OEToolkits 2.0.5Cc1c(cn(n1)C)c2cc(c(nc2)N)OC(C)c3cc(ccc3C(=O)N(C)C)F
FormulaC21 H24 F N5 O2
Name2-[(1~{R})-1-[2-azanyl-5-(1,3-dimethylpyrazol-4-yl)pyridin-3-yl]oxyethyl]-4-fluoranyl-~{N},~{N}-dimethyl-benzamide
ChEMBLCHEMBL3286810
DrugBank
ZINCZINC000169352667
PDB chain5kz0 Chain A Residue 1501 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB5kz0 Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations.
Resolution2.3 Å
Binding residue
(original residue number in PDB)		L1122 H1124 G1125 V1130 A1148 M1199 G1202 L1256 G1269 D1270
Binding residue
(residue number reindexed from 1)		L30 H32 G33 V38 A48 M99 G102 L156 G169 D170
Annotation score1
Binding affinityMOAD: Ki=22nM
PDBbind-CN: -logKd/Ki=7.66,Ki=22nM
BindingDB: Ki=22nM
Enzymatic activity
Catalytic site (original residue number in PDB) D1249 A1251 R1253 N1254 D1270
Catalytic site (residue number reindexed from 1) D149 A151 R153 N154 D170
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
Cellular Component
GO:0016020 membrane

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:5kz0, PDBe:5kz0, PDBj:5kz0
PDBsum5kz0
PubMed24819116
UniProtQ9UM73|ALK_HUMAN ALK tyrosine kinase receptor (Gene Name=ALK)

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