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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'''
| | ===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. | | The line below this paragraph, {{ABSTRACT_PUBMED_17289592}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17289592 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17289592}} |
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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]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:39:34 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:05:14 2008'' |
