2od7
From Proteopedia
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Crystal Structure of yHst2 bound to the intermediate analogue ADP-HPD, and and aceylated H4 peptide
Overview
The Sir2 family of proteins consists of broadly conserved NAD(+)-dependent, deacetylases that are implicated in diverse biological processes, including DNA regulation, metabolism, and longevity. Sir2 proteins are, regulated in part by the cellular concentrations of a noncompetitive, inhibitor, nicotinamide, that reacts with a Sir2 reaction intermediate via, a base-exchange reaction to reform NAD(+) at the expense of deacetylation., To gain a mechanistic understanding of nicotinamide inhibition in Sir2, enzymes, we captured the structure of nicotinamide bound to a Sir2, homolog, yeast Hst2, in complex with its acetyl-lysine 16 histone H4, substrate and a reaction intermediate analog, ADP-HPD. Together with, related biochemical studies and structures, we identify a nicotinamide, inhibition and base-exchange site that is distinct from the so-called "C, pocket" binding site for the nicotinamide group of NAD(+). These results, provide insights into the Sir2 mechanism of nicotinamide inhibition and, have important implications for the development of Sir2-specific, effectors.
About this Structure
2OD7 is a Single protein structure of sequence from Saccharomyces cerevisiae with ZN and A1R as ligands. Full crystallographic information is available from OCA.
Reference
Structural basis for nicotinamide inhibition and base exchange in Sir2 enzymes., Sanders BD, Zhao K, Slama JT, Marmorstein R, Mol Cell. 2007 Feb 9;25(3):463-72. PMID:17289592
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