Structural basis for the NAD-dependent deacetylase mechanism of Sir2.
J Biol Chem
; 277(37): 34489-98, 2002 Sep 13.
Article
em En
| MEDLINE
| ID: mdl-12091395
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Archaea
/
Sirtuínas
/
Proteínas Reguladoras de Informação Silenciosa de Saccharomyces cerevisiae
/
Histona Desacetilases
/
NAD
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Coréia do Sul