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2qqf

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{{STRUCTURE_2qqf| PDB=2qqf | SCENE= }}
{{STRUCTURE_2qqf| PDB=2qqf | SCENE= }}
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'''Hst2 bound to ADP-HPD and Acetylated histone H4'''
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===Hst2 bound to ADP-HPD and Acetylated histone H4===
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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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(as it appears on PubMed at http://www.pubmed.gov), where 17289592 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17289592}}
==About this Structure==
==About this Structure==
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[[Category: Transcription regulation]]
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[[Category: Zinc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 15:25:16 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 22:26:34 2008''

Revision as of 19:26, 27 July 2008

Image:2qqf.png

Template:STRUCTURE 2qqf

Hst2 bound to ADP-HPD and Acetylated histone H4

Template:ABSTRACT PUBMED 17289592

About this Structure

2QQF is a Protein complex structure of sequences 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

Page seeded by OCA on Sun Jul 27 22:26:34 2008

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