Structure of PDB 4rg0 Chain A Binding Site BS01

Receptor Information
>4rg0 Chain A (length=263) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
EIDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGSMSEDEFIEE
AKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREARHAFQT
QQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRY
VLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGK
MPYERFTNSETAEHIAQGLRLYRPHLASAAVYTIMYSCWHEKADERPTFK
ILLSNILDVMDEE
Ligand information
Ligand ID3P0
InChIInChI=1S/C36H38FN7O3/c1-36(2,22-38)25-16-23-10-11-44(35(47)33(23)29(37)18-25)31-7-5-6-27(28(31)21-45)24-17-30(34(46)42(4)20-24)40-32-9-8-26(19-39-32)43-14-12-41(3)13-15-43/h5-9,16-20,45H,10-15,21H2,1-4H3,(H,39,40)
InChIKeyAGMLIXLHTZGRPZ-UHFFFAOYSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CC(C)(C#N)c1cc2c(c(c1)F)C(=O)N(CC2)c3cccc(c3CO)C4=CN(C(=O)C(=C4)Nc5ccc(cn5)N6CCN(CC6)C)C
ACDLabs 12.01N#CC(c5cc(F)c6C(=O)N(c1cccc(c1CO)C=2C=C(C(=O)N(C=2)C)Nc4ncc(N3CCN(C)CC3)cc4)CCc6c5)(C)C
CACTVS 3.385CN1CCN(CC1)c2ccc(NC3=CC(=CN(C)C3=O)c4cccc(N5CCc6cc(cc(F)c6C5=O)C(C)(C)C#N)c4CO)nc2
FormulaC36 H38 F N7 O3
Name2-{8-fluoro-2-[2-(hydroxymethyl)-3-(1-methyl-5-{[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino}-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl}-2-methylpropanenitrile
ChEMBLCHEMBL3358341
DrugBank
ZINCZINC000116940301
PDB chain4rg0 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

[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
PDB4rg0 Finding the perfect spot for fluorine: Improving potency up to 40-fold during a rational fluorine scan of a Bruton's Tyrosine Kinase (BTK) inhibitor scaffold.
Resolution2.5 Å
Binding residue
(original residue number in PDB)		L408 G411 V416 A428 K430 Y476 M477 A478 G480 N526 L528 D539
Binding residue
(residue number reindexed from 1)		L13 G16 V21 A33 K35 Y81 M82 A83 G85 N131 L133 D144
Annotation score1
Binding affinityMOAD: ic50=50nM
PDBbind-CN: -logKd/Ki=7.30,IC50=50nM
BindingDB: IC50=50nM
Enzymatic activity
Catalytic site (original residue number in PDB) D521 A523 R525 N526 D539 F559
Catalytic site (residue number reindexed from 1) D126 A128 R130 N131 D144 F164
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:4rg0, PDBe:4rg0, PDBj:4rg0
PDBsum4rg0
PubMed25466710
UniProtQ06187|BTK_HUMAN Tyrosine-protein kinase BTK (Gene Name=BTK)

[Back to BioLiP]