1M2H

Sir2 homologue S24A mutant-ADP ribose complex

Summary for 1M2H

• Entry DOI: 10.2210/pdb1m2h/pdb
• Related: 1M2G 1M2J 1M2K 1M2N
• Descriptor: Silent Information Regulator 2, ZINC ION, ADENOSINE-5-DIPHOSPHORIBOSE, ... (4 entities in total)
• Functional Keywords: protein-ligand complex, gene regulation
• Biological source: Archaeoglobus fulgidus
• Cellular location: Cytoplasm (Probable): O28597
• Total number of polymer chains: 1
• Total formula weight: 28259.73

Authors

Chang, J.,Cho, Y. (deposition date: 2002-06-24, release date: 2003-04-08, Last modification date: 2024-05-29)

Primary citation

Chang, J.H.,Kim, H.C.,Hwang, K.Y.,Lee, J.W.,Jackson, S.P.,Bell, S.D.,Cho, Y.
Structural basis for the NAD-dependent deacetylase mechanism of Sir2
J.BIOL.CHEM., 277:34489-34498, 2002

PubMed 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.

PubMed: 12091395
DOI: 10.1074/jbc.M205460200

Experimental method

X-RAY DIFFRACTION (1.8 Å)