Structure of PDB 5aa8 Chain A Binding Site BS01

Receptor Information
>5aa8 Chain A (length=292) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
NPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGEVYEGQVPLQVAVKTLP
EVYSEQDELDFLMEALIISKFNHQNIVRCIGVSLQSLPRFILLEFMAGGD
LKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAAR
NCLLTCPGPGRVAKIGDFGMARDIYRGGCAMLPVKWMPPEAFMEGIFTSK
TDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVY
RIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEY
Ligand information
Ligand ID5P8
InChIInChI=1S/C21H19FN6O2/c1-11-15-7-13(22)4-5-14(15)21(29)27(2)10-16-19(17(8-23)28(3)26-16)12-6-18(30-11)20(24)25-9-12/h4-7,9,11H,10H2,1-3H3,(H2,24,25)/t11-/m1/s1
InChIKeyIIXWYSCJSQVBQM-LLVKDONJSA-N
SMILES
SoftwareSMILES
CACTVS 3.385C[CH]1Oc2cc(cnc2N)c3c(CN(C)C(=O)c4ccc(F)cc14)nn(C)c3C#N
ACDLabs 12.01C(#N)c4c3c1cc(c(nc1)N)OC(c2cc(ccc2C(N(Cc3nn4C)C)=O)F)C
CACTVS 3.385C[C@H]1Oc2cc(cnc2N)c3c(CN(C)C(=O)c4ccc(F)cc14)nn(C)c3C#N
OpenEye OEToolkits 1.7.6C[C@@H]1c2cc(ccc2C(=O)N(Cc3c(c(n(n3)C)C#N)-c4cc(c(nc4)N)O1)C)F
OpenEye OEToolkits 1.7.6CC1c2cc(ccc2C(=O)N(Cc3c(c(n(n3)C)C#N)-c4cc(c(nc4)N)O1)C)F
FormulaC21 H19 F N6 O2
Name(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
ChEMBLCHEMBL3286830
DrugBankDB12130
ZINCZINC000098208524
PDB chain5aa8 Chain A Residue 2402 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB5aa8 Resensitization to Crizotinib by the Lorlatinib Alk Resistance Mutation L1198F.
Resolution1.86 Å
Binding residue
(original residue number in PDB)		L1122 G1123 A1148 L1196 F1198 M1199 G1202 N1254 L1256 G1269 D1270 Y1401
Binding residue
(residue number reindexed from 1)		L30 G31 A45 L93 F95 M96 G99 N151 L153 G166 D167 Y292
Annotation score1
Binding affinityMOAD: Ki=8.6nM
PDBbind-CN: -logKd/Ki=8.07,Ki=8.6nM
Enzymatic activity
Catalytic site (original residue number in PDB) D1249 A1251 R1253 N1254 D1270 L1291
Catalytic site (residue number reindexed from 1) D146 A148 R150 N151 D167 L182
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:5aa8, PDBe:5aa8, PDBj:5aa8
PDBsum5aa8
PubMed26698910
UniProtQ9UM73|ALK_HUMAN ALK tyrosine kinase receptor (Gene Name=ALK)

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