Structure of PDB 3sfh Chain A Binding Site BS05

Receptor Information
>3sfh Chain A (length=342) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
LVPVYIYSPEYVSMCDSLAKIPKRASMVHSLIEAYALHKQMRIVKPKVAS
MEEMATFHTDAYLQHLQKVSQGIFDYAAAIGGATITAAQCLIDGMCKVAI
NWSGGWHHAKKDEASGFCYLNDAVLGILRLRRKFERILYVDLDLHHGDGV
EDAFSFTSKVMTVSLHKFSPGFFPGTGDVSDVGLGKGRYYSVNVPIQDGI
QDEKYYQICESVLKEVYQAFNPKAVVLQLGADTIAGDPMCSFNMTPVGIG
KCLKYILQWQLATLILGGGGYNLANTARCWTYLTGVILGKTLSSEIPDHE
FFTAYGPDYVLEITPSCRPDRNEPHRIQQILNYIKGNLKHVV
Ligand information
Ligand ID1DI
InChIInChI=1S/C17H16Cl2N2O/c18-14-6-5-11(15(19)8-14)7-16(20)17(22)21-9-12-3-1-2-4-13(12)10-21/h1-6,8,16H,7,9-10,20H2/t16-/m1/s1
InChIKeyJFWNERIMAUEHNN-MRXNPFEDSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.2c1ccc2c(c1)CN(C2)C(=O)C(Cc3ccc(cc3Cl)Cl)N
CACTVS 3.370N[C@H](Cc1ccc(Cl)cc1Cl)C(=O)N2Cc3ccccc3C2
OpenEye OEToolkits 1.7.2c1ccc2c(c1)CN(C2)C(=O)[C@@H](Cc3ccc(cc3Cl)Cl)N
CACTVS 3.370N[CH](Cc1ccc(Cl)cc1Cl)C(=O)N2Cc3ccccc3C2
ACDLabs 12.01Clc1ccc(c(Cl)c1)CC(N)C(=O)N3Cc2ccccc2C3
FormulaC17 H16 Cl2 N2 O
Name(2R)-2-amino-3-(2,4-dichlorophenyl)-1-(1,3-dihydro-2H-isoindol-2-yl)propan-1-one
ChEMBLCHEMBL1812335
DrugBank
ZINCZINC000072105413
PDB chain3sfh Chain A Residue 501 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB3sfh Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors.
Resolution2.7 Å
Binding residue
(original residue number in PDB)		I34 R37 G140 W141 H142 H143 G151 F152 H180 F208 G303 G304
Binding residue
(residue number reindexed from 1)		I21 R24 G105 W106 H107 H108 G116 F117 H145 F173 G268 G269
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=7.05,IC50=90nM
BindingDB: IC50=90nM
Enzymatic activity
Enzyme Commision number 3.5.1.-
3.5.1.98: histone deacetylase.
Gene Ontology
Molecular Function
GO:0004407 histone deacetylase activity
GO:0005515 protein binding
GO:0016787 hydrolase activity
GO:0030544 Hsp70 protein binding
GO:0033558 protein lysine deacetylase activity
GO:0046872 metal ion binding
GO:0051879 Hsp90 protein binding
GO:0140297 DNA-binding transcription factor binding
GO:0160008 protein decrotonylase activity
GO:0160009 histone decrotonylase activity
Biological Process
GO:0000122 negative regulation of transcription by RNA polymerase II
GO:0006325 chromatin organization
GO:0007064 mitotic sister chromatid cohesion
GO:0031397 negative regulation of protein ubiquitination
GO:0031647 regulation of protein stability
GO:0032204 regulation of telomere maintenance
GO:0040029 epigenetic regulation of gene expression
Cellular Component
GO:0000118 histone deacetylase complex
GO:0000228 nuclear chromosome
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0005737 cytoplasm

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Molecular Function
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Biological Process
View graph for
Cellular Component
External links
PDB RCSB:3sfh, PDBe:3sfh, PDBj:3sfh
PDBsum3sfh
PubMed21723733
UniProtQ9BY41|HDAC8_HUMAN Histone deacetylase 8 (Gene Name=HDAC8)

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