Structure of PDB 4otf Chain A Binding Site BS01

Receptor Information
>4otf 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
AKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRHRFQT
QQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRY
VLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGK
MPYERFTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFK
ILLSNILDVMDEN
Ligand information
Ligand ID2VL
InChIInChI=1S/C33H36N6O3S/c1-20-24(9-7-10-25(20)36-31(40)28-18-22-8-5-6-11-27(22)43-28)26-19-39(4)33(42)30(35-26)34-23-14-12-21(13-15-23)29-32(41)38(3)17-16-37(29)2/h7,9-10,12-15,18-19,29H,5-6,8,11,16-17H2,1-4H3,(H,34,35)(H,36,40)/t29-/m1/s1
InChIKeyCDOOFZZILLRUQH-GDLZYMKVSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6Cc1c(cccc1NC(=O)c2cc3c(s2)CCCC3)C4=CN(C(=O)C(=N4)Nc5ccc(cc5)[C@@H]6C(=O)N(CCN6C)C)C
CACTVS 3.385CN1CCN(C)C(=O)[C@H]1c2ccc(NC3=NC(=CN(C)C3=O)c4cccc(NC(=O)c5sc6CCCCc6c5)c4C)cc2
OpenEye OEToolkits 1.7.6Cc1c(cccc1NC(=O)c2cc3c(s2)CCCC3)C4=CN(C(=O)C(=N4)Nc5ccc(cc5)C6C(=O)N(CCN6C)C)C
CACTVS 3.385CN1CCN(C)C(=O)[CH]1c2ccc(NC3=NC(=CN(C)C3=O)c4cccc(NC(=O)c5sc6CCCCc6c5)c4C)cc2
ACDLabs 12.01O=C1N(C)CCN(C)C1c2ccc(cc2)NC3=NC(=CN(C3=O)C)c4cccc(c4C)NC(=O)c5sc6c(c5)CCCC6
FormulaC33 H36 N6 O3 S
NameN-{3-[6-({4-[(2R)-1,4-dimethyl-3-oxopiperazin-2-yl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl }-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;
GDC0834
ChEMBLCHEMBL2057915
DrugBank
ZINCZINC000059185874
PDB chain4otf Chain A Residue 704 [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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PDB4otf Potent and selective Bruton's tyrosine kinase inhibitors: Discovery of GDC-0834.
Resolution1.95 Å
Binding residue
(original residue number in PDB)		L408 T410 G411 Q412 F413 V416 A428 K430 Y476 M477 G480 L528 D539
Binding residue
(residue number reindexed from 1)		L13 T15 G16 Q17 F18 V21 A33 K35 Y81 M82 G85 L133 D144
Annotation score1
Binding affinityMOAD: ic50=0.006uM
PDBbind-CN: -logKd/Ki=8.22,IC50=0.006uM
BindingDB: IC50=6.0nM,EC50=380nM
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:4otf, PDBe:4otf, PDBj:4otf
PDBsum4otf
PubMed25701252
UniProtQ06187|BTK_HUMAN Tyrosine-protein kinase BTK (Gene Name=BTK)

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