2h4h: Difference between revisions

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[[Image:2h4h.gif|left|200px]]
{{Seed}}
[[Image:2h4h.png|left|200px]]


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{{STRUCTURE_2h4h|  PDB=2h4h  |  SCENE=  }}  
{{STRUCTURE_2h4h|  PDB=2h4h  |  SCENE=  }}  


'''Sir2 H116Y mutant-p53 peptide-NAD'''
===Sir2 H116Y mutant-p53 peptide-NAD===




==Overview==
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Sirtuin proteins comprise a unique class of NAD+-dependent protein deacetylases. Although several structures of sirtuins have been determined, the mechanism by which NAD+ cleavage occurs has remained unclear. We report the structures of ternary complexes containing NAD+ and acetylated peptide bound to the bacterial sirtuin Sir2Tm and to a catalytic mutant (Sir2Tm(H116Y)). NAD+ in these structures binds in a conformation different from that seen in previous structures, exposing the alpha face of the nicotinamide ribose to the carbonyl oxygen of the acetyl lysine substrate. The NAD+ conformation is identical in both structures, suggesting that proper coenzyme orientation is not dependent on contacts with the catalytic histidine. We also present the structure of Sir2Tm(H116A) bound to deacteylated peptide and 3'-O-acetyl ADP ribose. Taken together, these structures suggest a mechanism for nicotinamide cleavage in which an invariant phenylalanine plays a central role in promoting formation of the O-alkylamidate reaction intermediate and preventing nicotinamide exchange.
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{{ABSTRACT_PUBMED_16905097}}


==About this Structure==
==About this Structure==
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[[Category: Rossmann fold]]
[[Category: Rossmann fold]]
[[Category: Zn-binding domain]]
[[Category: Zn-binding domain]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 05:51:19 2008''
 
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Revision as of 21:18, 28 July 2008

File:2h4h.png

Template:STRUCTURE 2h4h

Sir2 H116Y mutant-p53 peptide-NAD

Template:ABSTRACT PUBMED 16905097

About this Structure

2H4H is a Protein complex structure of sequences from Thermotoga maritima. Full crystallographic information is available from OCA.

Reference

Insights into the sirtuin mechanism from ternary complexes containing NAD+ and acetylated peptide., Hoff KG, Avalos JL, Sens K, Wolberger C, Structure. 2006 Aug;14(8):1231-40. PMID:16905097

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