1m2j
Sir2 homologue H80N mutant-ADP ribose complex
Structural highlights
FunctionNPD1_ARCFU NAD-dependent lysine deacetylase and desuccinylase that specifically removes acetyl and succinyl groups on target proteins. Modulates the activities of several proteins which are inactive in their acylated form. Deacetylates the N-terminal lysine residue of Alba, the major archaeal chromatin protein and that, in turn, increases Alba's DNA binding affinity, thereby repressing transcription (By similarity).[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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