Molecular Basis for the Selective Inhibition of Histone Deacetylase 6 by a Mercaptoacetamide Inhibitor

. 2018 Dec 13 ; 9 (12) : 1301-1305. [epub] 20181121

Status PubMed-not-MEDLINE Jazyk angličtina Země Spojené státy americké Médium electronic-ecollection

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid30613344

Grantová podpora
P41 GM103403 NIGMS NIH HHS - United States
R01 GM049758 NIGMS NIH HHS - United States

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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