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==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.

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==

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[[Category: Saccharomyces cerevisiae]]

[[Category: Marmorstein, R.]]

[[Category: Sanders, B.D.]]

[[Category: Sanders, B D.]]

[[Category: Slama, J.]]

[[Category: Zhao, K.]]

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[[Category: zinc]]

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@@ Line 4: / Line 4: @@
 ==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.
+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==
@@ Line 14: / Line 14: @@
 [[Category: Saccharomyces cerevisiae]]
 [[Category: Marmorstein, R.]]
-[[Category: Sanders, B.D.]]
+[[Category: Sanders, B D.]]
 [[Category: Slama, J.]]
 [[Category: Zhao, K.]]
@@ Line 32: / Line 32: @@
 [[Category: zinc]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:51:03 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:41:22 2008''