6MR5

Crystal Structure of Danio rerio histone deacetylase 6 catalytic domain 2 in complex with a mercaptoacetamide-based inhibitor

Summary for 6MR5

• Entry DOI: 10.2210/pdb6mr5/pdb
• Descriptor: Hdac6 protein, ZINC ION, POTASSIUM ION, ... (8 entities in total)
• Functional Keywords: histone deacetylase, zinc hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Danio rerio (Zebrafish)
• Total number of polymer chains: 2
• Total formula weight: 82012.16

Authors

Porter, N.J.,Christianson, D.W. (deposition date: 2018-10-11, release date: 2018-12-05, Last modification date: 2024-03-13)

Primary citation

Porter, N.J.,Shen, S.,Barinka, C.,Kozikowski, A.P.,Christianson, D.W.
Molecular Basis for the Selective Inhibition of Histone Deacetylase 6 by a Mercaptoacetamide Inhibitor.
ACS Med Chem Lett, 9:1301-1305, 2018

PubMed Abstract: 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.

PubMed: 30613344
DOI: 10.1021/acsmedchemlett.8b00487

Experimental method

X-RAY DIFFRACTION (1.85 Å)