Structure of PDB 4rx5 Chain A Binding Site BS01

Receptor Information
>4rx5 Chain A (length=265) 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
FKILLSNILDVMDEN
Ligand information
Ligand ID3YO
InChIInChI=1S/C27H24FN7O2S/c1-15-18(7-8-19(28)25(15)30-27(37)23-11-16-5-3-4-6-22(16)38-23)20-13-21(26(36)32-31-20)29-24-12-17-14-34(2)9-10-35(17)33-24/h3-8,11-13H,9-10,14H2,1-2H3,(H,30,37)(H,32,36)(H,29,31,33)
InChIKeyMZSDTUIZKGUVHK-UHFFFAOYSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6Cc1c(ccc(c1NC(=O)c2cc3ccccc3s2)F)C4=NNC(=O)C(=C4)Nc5cc6n(n5)CCN(C6)C
CACTVS 3.385CN1CCn2nc(NC3=CC(=NNC3=O)c4ccc(F)c(NC(=O)c5sc6ccccc6c5)c4C)cc2C1
ACDLabs 12.01O=C3C(Nc1nn2c(c1)CN(C)CC2)=CC(=NN3)c4c(c(c(F)cc4)NC(=O)c6sc5ccccc5c6)C
FormulaC27 H24 F N7 O2 S
NameN-(6-fluoro-2-methyl-3-{5-[(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl)amino]-6-oxo-1,6-dihydropyridazin-3-yl}phenyl)-1-benzothiophene-2-carboxamide
ChEMBLCHEMBL3746293
DrugBank
ZINCZINC000068207013
PDB chain4rx5 Chain A Residue 706 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4rx5 Discovery of highly potent and selective Bruton's tyrosine kinase inhibitors: Pyridazinone analogs with improved metabolic stability.
Resolution1.356 Å
Binding residue
(original residue number in PDB)		L408 T410 G411 F413 V416 K430 Y476 M477 A478 G480 L528 D539
Binding residue
(residue number reindexed from 1)		L15 T17 G18 F20 V23 K37 Y83 M84 A85 G87 L135 D146
Annotation score1
Binding affinityMOAD: ic50=3nM
PDBbind-CN: -logKd/Ki=8.52,IC50=3nM
BindingDB: IC50=3.0nM
Enzymatic activity
Catalytic site (original residue number in PDB) D521 A523 R525 N526 D539 F559
Catalytic site (residue number reindexed from 1) D128 A130 R132 N133 D146 F166
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:4rx5, PDBe:4rx5, PDBj:4rx5
PDBsum4rx5
PubMed26675441
UniProtQ06187|BTK_HUMAN Tyrosine-protein kinase BTK (Gene Name=BTK)

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