Structure of PDB 3sff Chain A Binding Site BS01

Receptor Information
>3sff Chain A (length=341) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
LVPVYIYSPEYVSMCDSLAKIPKRASMVHSLIEAYALHKQMRIVKPKVAS
MEEMATFHTDAYLQHLQKVSGIFDYAAAIGGATITAAQCLIDGMCKVAIN
WSGGWHHAKKDEASGFCYLNDAVLGILRLRRKFERILYVDLDLHHGDGVE
DAFSFTSKVMTVSLHKFSPGFFPGTGDVSDVGLGKGRYYSVNVPIQDGIQ
DEKYYQICESVLKEVYQAFNPKAVVLQLGADTIAGDPMCSFNMTPVGIGK
CLKYILQWQLATLILGGGGYNLANTARCWTYLTGVILGKTLSSEIPDHEF
FTAYGPDYVLEITPSCRPDRNEPHRIQQILNYIKGNLKHVV
Ligand information
Ligand ID0DI
InChIInChI=1S/C20H20ClF2N3O2/c21-14-3-1-2-13(10-14)11-18(24)20(28)26-8-6-25(7-9-26)19(27)16-12-15(22)4-5-17(16)23/h1-5,10,12,18H,6-9,11,24H2/t18-/m1/s1
InChIKeyNASCAWUSOSJBJH-GOSISDBHSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.2c1cc(cc(c1)Cl)CC(C(=O)N2CCN(CC2)C(=O)c3cc(ccc3F)F)N
OpenEye OEToolkits 1.7.2c1cc(cc(c1)Cl)C[C@H](C(=O)N2CCN(CC2)C(=O)c3cc(ccc3F)F)N
CACTVS 3.370N[CH](Cc1cccc(Cl)c1)C(=O)N2CCN(CC2)C(=O)c3cc(F)ccc3F
CACTVS 3.370N[C@H](Cc1cccc(Cl)c1)C(=O)N2CCN(CC2)C(=O)c3cc(F)ccc3F
ACDLabs 12.01O=C(N2CCN(C(=O)c1cc(F)ccc1F)CC2)C(N)Cc3cccc(Cl)c3
FormulaC20 H20 Cl F2 N3 O2
Name(2R)-2-amino-3-(3-chlorophenyl)-1-[4-(2,5-difluorobenzoyl)piperazin-1-yl]propan-1-one
ChEMBLCHEMBL1812334
DrugBank
ZINCZINC000072105412
PDB chain3sff Chain A Residue 378 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB3sff Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors.
Resolution2.0 Å
Binding residue
(original residue number in PDB)		I34 G140 W141 H142 H143 G151 F152 C153 D178 H180 F208 G303 G304 Y306
Binding residue
(residue number reindexed from 1)		I21 G104 W105 H106 H107 G115 F116 C117 D142 H144 F172 G267 G268 Y270
Annotation score1
Binding affinityMOAD: ic50=200nM
PDBbind-CN: -logKd/Ki=6.70,IC50=200nM
BindingDB: IC50=200nM
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
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Cellular Component
External links
PDB RCSB:3sff, PDBe:3sff, PDBj:3sff
PDBsum3sff
PubMed21723733
UniProtQ9BY41|HDAC8_HUMAN Histone deacetylase 8 (Gene Name=HDAC8)

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