Structure of PDB 4rfm Chain A Binding Site BS01

Receptor Information
>4rfm Chain A (length=249) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
SVIDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIE
EAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFA
AETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVIKVSDFGMTR
FPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVE
DISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAAIAAS
Ligand information
Ligand ID3P6
InChIInChI=1S/C25H27F2N5O3S/c1-24-12-18-17(11-20(24)25(24,26)27)21(31-30-18)23(33)29-16-13-28-32(14-16)22(15-7-3-2-4-8-15)19-9-5-6-10-36(19,34)35/h2-4,7-8,13-14,19-20,22H,5-6,9-12H2,1H3,(H,29,33)(H,30,31)/t19-,20+,22-,24-/m1/s1
InChIKeyJNRFIKALOWSUBG-DAVFGYKESA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6C[C@@]12Cc3c(c(n[nH]3)C(=O)Nc4cnn(c4)[C@H](c5ccccc5)[C@H]6CCCCS6(=O)=O)C[C@@H]1C2(F)F
OpenEye OEToolkits 1.7.6CC12Cc3c(c(n[nH]3)C(=O)Nc4cnn(c4)C(c5ccccc5)C6CCCCS6(=O)=O)CC1C2(F)F
CACTVS 3.385C[C]12Cc3[nH]nc(C(=O)Nc4cnn(c4)[CH]([CH]5CCCC[S]5(=O)=O)c6ccccc6)c3C[CH]1C2(F)F
CACTVS 3.385C[C@@]12Cc3[nH]nc(C(=O)Nc4cnn(c4)[C@@H]([C@H]5CCCC[S]5(=O)=O)c6ccccc6)c3C[C@@H]1C2(F)F
ACDLabs 12.01O=S6(=O)C(C(c1ccccc1)n5ncc(NC(=O)c2nnc4c2CC3C(F)(F)C3(C)C4)c5)CCCC6
FormulaC25 H27 F2 N5 O3 S
Name(4aS,5aR)-N-{1-[(R)-[(2R)-1,1-dioxidotetrahydro-2H-thiopyran-2-yl](phenyl)methyl]-1H-pyrazol-4-yl}-5,5-difluoro-5a-methyl-1,4,4a,5,5a,6-hexahydrocyclopropa[f]indazole-3-carboxamide
ChEMBLCHEMBL3426309
DrugBank
ZINC
PDB chain4rfm Chain A Residue 701 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4rfm Tetrahydroindazoles as Interleukin-2 Inducible T-Cell Kinase Inhibitors. Part II. Second-Generation Analogues with Enhanced Potency, Selectivity, and Pharmacodynamic Modulation in Vivo.
Resolution2.1 Å
Binding residue
(original residue number in PDB)		I369 F374 A389 K391 F435 E436 F437 M438 E439 H440 G441 L489
Binding residue
(residue number reindexed from 1)		I14 F19 A34 K36 F80 E81 F82 M83 E84 H85 G86 L134
Annotation score1
Binding affinityMOAD: Ki=0.00009uM
PDBbind-CN: -logKd/Ki=10.05,Ki=90pM
BindingDB: IC50=4.0nM,Ki=0.090000nM
Enzymatic activity
Catalytic site (original residue number in PDB) D482 A484 R486 N487 D500 P521
Catalytic site (residue number reindexed from 1) D127 A129 R131 N132 D145 P152
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:0004715 non-membrane spanning 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:4rfm, PDBe:4rfm, PDBj:4rfm
PDBsum4rfm
PubMed25844760
UniProtQ08881|ITK_HUMAN Tyrosine-protein kinase ITK/TSK (Gene Name=ITK)

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