Molecular Basis for the Selective Inhibition of Histone Deacetylase 6 by a Mercaptoacetamide Inhibitor
Status PubMed-not-MEDLINE Jazyk angličtina Země Spojené státy americké Médium electronic-ecollection
Typ dokumentu časopisecké články
Grantová podpora
P41 GM103403
NIGMS NIH HHS - United States
R01 GM049758
NIGMS NIH HHS - United States
PubMed
30613344
PubMed Central
PMC6295862
DOI
10.1021/acsmedchemlett.8b00487
Knihovny.cz E-zdroje
- Publikační typ
- časopisecké články MeSH
Mercaptoacetamide histone deacetylase inhibitors are neuroprotective agents that do not exhibit the genotoxicity associated with more commonly used hydroxamate inhibitors. Here, we present the crystal structure of a selective mercaptoacetamide complexed with the C-terminal catalytic domain of HDAC6. When compared with the structure of a mercaptoacetamide bound to the class I isozyme HDAC8, different interactions are observed with the conserved tandem histidine pair in the active site. These differences likely contribute to the selectivity for inhibition of HDAC6, an important target for cancer chemotherapy and the treatment of neurodegenerative disease.
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