Download MendeleyStructural Snapshots of Human HDAC8 Provide Insights into the Class I Histone Deacetylases
Somoza, J.R., Skene, R.J., Katz, B.A., Mol, C., Ho, J.D., Jennings, A.J., Luong, C., Arvai, A., Buggy, J.J., Chi, E., Tang, J., Sang, B.-C., Verner, E., Wynands, R., Leahy, E.M., Dougan, D.R., Snell, G., Navre, M., Knuth, M.W., Swanson, R.V., McRee, D.E., Tari, L.W.(2004) Structure 12: 1325-1334
- PubMed: 15242608
- DOI: https://doi.org/10.1016/j.str.2004.04.012
- Primary Citation of Related Structures:
1T64, 1T67, 1T69, 1VKG - PubMed 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.
Organizational Affiliation:
Celera, 180 Kimball Way, South San Francisco, CA 94080 USA. [email protected]
