Structure of PDB 6x3p Chain A Binding Site BS01

Receptor Information
>6x3p Chain A (length=266) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
SWEIDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGSMSEDEFI
EEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRHRF
QTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLS
RYVLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSL
GKMPYERFTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADERPT
FKILLSNILDVMDEES
Ligand information
Ligand IDUM4
InChIInChI=1S/C30H28F3N7O3/c31-30(32,33)18-9-10-35-23(14-18)37-29(42)16-2-7-21(22(13-16)43-20-5-6-20)25-26-27(34)36-11-12-39(26)28(38-25)17-1-3-19-4-8-24(41)40(19)15-17/h2,7,9-14,17,19-20H,1,3-6,8,15H2,(H2,34,36)(H,35,37,42)/t17-,19+/m1/s1
InChIKeyWMMNTQFZCHUZSM-MJGOQNOKSA-N
SMILES
SoftwareSMILES
CACTVS 3.385Nc1nccn2c(nc(c3ccc(cc3OC4CC4)C(=O)Nc5cc(ccn5)C(F)(F)F)c12)[C@@H]6CC[C@H]7CCC(=O)N7C6
ACDLabs 12.01n1c(c2c(nc(n2cc1)C3CCC4N(C3)C(CC4)=O)c6ccc(C(Nc5nccc(C(F)(F)F)c5)=O)cc6OC7CC7)N
OpenEye OEToolkits 2.0.7c1cc(c(cc1C(=O)Nc2cc(ccn2)C(F)(F)F)OC3CC3)c4c5c(nccn5c(n4)C6CCC7CCC(=O)N7C6)N
CACTVS 3.385Nc1nccn2c(nc(c3ccc(cc3OC4CC4)C(=O)Nc5cc(ccn5)C(F)(F)F)c12)[CH]6CC[CH]7CCC(=O)N7C6
OpenEye OEToolkits 2.0.7c1cc(c(cc1C(=O)Nc2cc(ccn2)C(F)(F)F)OC3CC3)c4c5c(nccn5c(n4)[C@@H]6CC[C@H]7CCC(=O)N7C6)N
FormulaC30 H28 F3 N7 O3
Name4-{8-amino-3-[(6R,8aS)-3-oxooctahydroindolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl}-3-(cyclopropyloxy)-N-[4-(trifluoromethyl)pyridin-2-yl]benzamide
ChEMBLCHEMBL4107779
DrugBank
ZINC
PDB chain6x3p Chain A Residue 701 [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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PDB6x3p Potent, non-covalent reversible BTK inhibitors with 8-amino-imidazo[1,5-a]pyrazine core featuring 3-position bicyclic ring substitutes.
Resolution1.34 Å
Binding residue
(original residue number in PDB)		L408 V416 A428 K430 F442 A446 L460 I472 T474 M477 G480 C481 N526 L528 S538 D539 F540 L542
Binding residue
(residue number reindexed from 1)		L15 V23 A35 K37 F49 A53 L67 I79 T81 M84 G87 C88 N133 L135 S145 D146 F147 L149
Annotation score1
Binding affinityMOAD: ic50=0.58nM
BindingDB: IC50=0.58nM
Enzymatic activity
Catalytic site (original residue number in PDB) D521 A523 R525 N526 D539
Catalytic site (residue number reindexed from 1) D128 A130 R132 N133 D146
Enzyme Commision number 2.7.10.2: non-specific 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

View graph for
Molecular Function
View graph for
Biological Process
External links
PDB RCSB:6x3p, PDBe:6x3p, PDBj:6x3p
PDBsum6x3p
PubMed32738973
UniProtQ06187|BTK_HUMAN Tyrosine-protein kinase BTK (Gene Name=BTK)

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