2od9

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{{STRUCTURE_2od9| PDB=2od9 | SCENE= }}
{{STRUCTURE_2od9| PDB=2od9 | SCENE= }}
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'''Structural Basis for Nicotinamide Inhibition and Base Exchange in Sir2 Enzymes'''
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===Structural Basis for Nicotinamide Inhibition and Base Exchange in Sir2 Enzymes===
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==Overview==
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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.
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==About this Structure==
==About this Structure==
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[[Category: Rossmann fold]]
[[Category: Rossmann fold]]
[[Category: Zn binding protein]]
[[Category: Zn binding protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:39:34 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:05:14 2008''

Revision as of 15:05, 27 July 2008

Image:2od9.png

Template:STRUCTURE 2od9

Structural Basis for Nicotinamide Inhibition and Base Exchange in Sir2 Enzymes

Template:ABSTRACT PUBMED 17289592

About this Structure

2OD9 is a Single protein structure of sequence from Saccharomyces cerevisiae. 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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