1m2h
From Proteopedia
Sir2 homologue S24A mutant-ADP ribose complex
Overview
The NAD-dependent histone/protein deacetylase activity of Sir2 (silent information regulator 2) accounts for its diverse biological roles including gene silencing, DNA damage repair, cell cycle regulation, and life span extension. We provide crystallographic evidence that 2'-O-acetyl ADP-ribose is the reaction product that is formed at the active site of Sir2 from the 2.6-A co-crystal structure of 2'-O-acetyl-ADP-ribose and Sir2 from Archaeoglobus fulgidus. In addition, we show that His-116 and Phe-159 play critical roles in the catalysis and substrate recognition. The conserved Ser-24 and Asp-101 contribute to the stability for NAD binding rather than being directly involved in the catalysis. The crystal structures of wild type and mutant derivatives of Sir2, in conjunction with biochemical analyses of the mutants, provide novel insights into the reaction mechanism of Sir2-mediated deacetylation.
About this Structure
1M2H is a Single protein structure of sequence from Archaeoglobus fulgidus. Full crystallographic information is available from OCA.
Reference
Structural basis for the NAD-dependent deacetylase mechanism of Sir2., Chang JH, Kim HC, Hwang KY, Lee JW, Jackson SP, Bell SD, Cho Y, J Biol Chem. 2002 Sep 13;277(37):34489-98. Epub 2002 Jun 28. PMID:12091395 Page seeded by OCA on Sat May 3 00:33:17 2008
