The yeast Sir2 (silent information regulator-2) protein functions as an NAD+-dependent histone deacetylase to silence gene expression from the mating-type locus, tolomeres and rDNA and also promotes longevity and genome stability in response to calorie restriction. Homologues of yeast Sir2 have been identified in the three domains of bacteria, archaea and eukaryotes; in mammalian cells, Sir2 proteins also deacetylate non-histone proteins such as the p53 tumour suppressor protein, α-tubulin and forkhead transcription factors to mediate diverse biological processes including metabolism, cell motility and cancer. We have determined the X-ray crystal structure of a Sir2 homologue from yeast Hst2 (yHst2), in various liganded forms, including the yHst2/acetyl-Lys-16 histone H4/NAD+ ternary complex; we have also performed related biochemical studies to address the conserved mode of catalysis by these enzymes as well as the distinguishing features that allow different members of the family to target their respective cognate substrates. These studies have implications for the structure-based design of Sir2-specific small molecule compounds, which might modulate Sir2 function for therapeutic application.
Skip Nav Destination
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article| October 26 2004
Structure and chemistry of the Sir2 family of NAD+-dependent histone/protein deactylases
R. Marmorstein 1
1The Wistar Institute and Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
Search for other works by this author on:
Biochem Soc Trans (2004) 32 (6): 904–909.
June 28 2004
R. Marmorstein; Structure and chemistry of the Sir2 family of NAD+-dependent histone/protein deactylases. Biochem Soc Trans 1 November 2004; 32 (6): 904–909. doi: https://doi.org/10.1042/BST0320904
Download citation file:
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your InstitutionSign in via your Institution
Get Access To This Article
Buy This Article