1yc5
From Proteopedia
Sir2-p53 peptide-nicotinamide
Structural highlights
FunctionNPD_THEMA NAD-dependent protein deacetylase which modulates the activities of several enzymes which are inactive in their acetylated form. Has also depropionylation activity in vitro. Also able to ADP-ribosylate peptide substrates with Arg or Lys in the +2 position. The role of this function in vivo is not clear.[1] [2] [3] 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 PubMedSir2 enzymes form a unique class of NAD(+)-dependent deacetylases required for diverse biological processes, including transcriptional silencing, regulation of apoptosis, fat mobilization, and lifespan regulation. Sir2 activity is regulated by nicotinamide, a noncompetitive inhibitor that promotes a base-exchange reaction at the expense of deacetylation. To elucidate the mechanism of nicotinamide inhibition, we determined ternary complex structures of Sir2 enzymes containing nicotinamide. The structures show that free nicotinamide binds in a conserved pocket that participates in NAD(+) binding and catalysis. Based on our structures, we engineered a mutant that deacetylates peptides by using nicotinic acid adenine dinucleotide (NAAD) as a cosubstrate and is inhibited by nicotinic acid. The characteristics of the altered specificity enzyme establish that Sir2 enzymes contain a single site that participates in catalysis and nicotinamide regulation and provides additional insights into the Sir2 catalytic mechanism. Mechanism of sirtuin inhibition by nicotinamide: altering the NAD(+) cosubstrate specificity of a Sir2 enzyme.,Avalos JL, Bever KM, Wolberger C Mol Cell. 2005 Mar 18;17(6):855-68. PMID:15780941[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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