| Literature DB >> 15242608 |
John R Somoza1, Robert J Skene, Bradley A Katz, Clifford Mol, Joseph D Ho, Andy J Jennings, Christine Luong, Andrew Arvai, Joseph J Buggy, Ellen Chi, Jie Tang, Bi-Ching Sang, Erik Verner, Robert Wynands, Ellen M Leahy, Douglas R Dougan, Gyorgy Snell, Marc Navre, Mark W Knuth, Ronald V Swanson, Duncan E McRee, Leslie W Tari.
Abstract
Modulation of the acetylation state of histones plays a pivotal role in the regulation of gene expression. Histone deacetylases (HDACs) catalyze the removal of acetyl groups from lysines near the N termini of histones. This reaction promotes the condensation of chromatin, leading to repression of transcription. HDAC deregulation has been linked to several types of cancer, suggesting a potential use for HDAC inhibitors in oncology. Here we describe the first crystal structures of a human HDAC: the structures of human HDAC8 complexed with four structurally diverse hydroxamate inhibitors. This work sheds light on the catalytic mechanism of the HDACs, and on differences in substrate specificity across the HDAC family. The structure also suggests how phosphorylation of Ser39 affects HDAC8 activity.Entities:
Mesh：
Substances：
Year: 2004 PMID： 15242608 DOI： 10.1016/j.str.2004.04.012
Source DB: PubMed Journal: Structure ISSN： 0969-2126 Impact factor: 5.006