2qqf

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spinqualitylabelsall models 2qqf, resolution 2.0Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Hst2 bound to ADP-HPD and Acetylated histone H4

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

2QQF is a Protein complex structure of sequences from Saccharomyces cerevisiae with and 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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