Structure of PDB 6dbm Chain A Binding Site BS01

Receptor Information
>6dbm Chain A (length=274) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
PTVFHKRYLKKIRDLGEGHFGKVSLYCYEMVAVKALKQHRSGWKQEIDIL
RTLYHEHIIKYKGCCEDAGAASLQLVMEYVPLGSLRDYLPRHSIGLAQLL
LFAQQICEGMAYLHSQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVPEG
HEYYRDGDSPVFWYAPECLKEYKFYYASDVWSFGVTLYELLTHCDSSQSP
PTKFLELIGIAQGQMTVLRLTELLERGERLPRPDKCPAEVYHLMKNCWET
EASFRPTFENLIPILKTVHEKYQG
Ligand information
Ligand IDG4J
InChIInChI=1S/C18H21F2N7O/c1-25-8-11(7-22-25)23-17-21-5-4-15(24-17)26-9-12-2-3-13(10-26)27(12)16(28)14-6-18(14,19)20/h4-5,7-8,12-14H,2-3,6,9-10H2,1H3,(H,21,23,24)/t12-,13+,14-/m0/s1
InChIKeyBUWBRTXGQRBBHG-MJBXVCDLSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 2.0.6Cn1cc(cn1)Nc2nccc(n2)N3C[C@H]4CC[C@@H](C3)N4C(=O)[C@@H]5CC5(F)F
ACDLabs 12.01N(c1nc(ccn1)N2CC3N(C(C2)CC3)C(C4C(F)(C4)F)=O)c5cnn(C)c5
CACTVS 3.385Cn1cc(Nc2nccc(n2)N3C[CH]4CC[CH](C3)N4C(=O)[CH]5CC5(F)F)cn1
CACTVS 3.385Cn1cc(Nc2nccc(n2)N3C[C@H]4CC[C@@H](C3)N4C(=O)[C@@H]5CC5(F)F)cn1
OpenEye OEToolkits 2.0.6Cn1cc(cn1)Nc2nccc(n2)N3CC4CCC(C3)N4C(=O)C5CC5(F)F
FormulaC18 H21 F2 N7 O
Name[(1S)-2,2-difluorocyclopropyl][(1R,5S)-3-{2-[(1-methyl-1H-pyrazol-4-yl)amino]pyrimidin-4-yl}-3,8-diazabicyclo[3.2.1]octan-8-yl]methanone
ChEMBLCHEMBL4297477
DrugBankDB15003
ZINCZINC000526061580
PDB chain6dbm Chain A Residue 4000 [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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PDB6dbm Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841).
Resolution2.368 Å
Binding residue
(original residue number in PDB)		L903 G904 E905 G906 V911 K930 I960 Y980 V981 G984 L1030 G1040 D1041
Binding residue
(residue number reindexed from 1)		L15 G16 E17 G18 V23 K34 I59 Y79 V80 G83 L129 G139 D140
Annotation score1
Binding affinityMOAD: ic50=23nM
BindingDB: IC50=23.0nM
Enzymatic activity
Catalytic site (original residue number in PDB) D1023 A1025 R1027 N1028 D1041 P1064
Catalytic site (residue number reindexed from 1) D122 A124 R126 N127 D140 P160
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
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Biological Process
External links
PDB RCSB:6dbm, PDBe:6dbm, PDBj:6dbm
PDBsum6dbm
PubMed30113844
UniProtP29597|TYK2_HUMAN Non-receptor tyrosine-protein kinase TYK2 (Gene Name=TYK2)

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