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| [[Image:1yc5.gif|left|200px]] | | {{Seed}} |
| | [[Image:1yc5.png|left|200px]] |
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| {{STRUCTURE_1yc5| PDB=1yc5 | SCENE= }} | | {{STRUCTURE_1yc5| PDB=1yc5 | SCENE= }} |
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| '''Sir2-p53 peptide-nicotinamide'''
| | ===Sir2-p53 peptide-nicotinamide=== |
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| ==Overview==
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| Sir2 enzymes form a unique class of NAD(+)-dependent deacetylases required for diverse biological processes, including transcriptional silencing, regulation of apoptosis, fat mobilization, and lifespan regulation. Sir2 activity is regulated by nicotinamide, a noncompetitive inhibitor that promotes a base-exchange reaction at the expense of deacetylation. To elucidate the mechanism of nicotinamide inhibition, we determined ternary complex structures of Sir2 enzymes containing nicotinamide. The structures show that free nicotinamide binds in a conserved pocket that participates in NAD(+) binding and catalysis. Based on our structures, we engineered a mutant that deacetylates peptides by using nicotinic acid adenine dinucleotide (NAAD) as a cosubstrate and is inhibited by nicotinic acid. The characteristics of the altered specificity enzyme establish that Sir2 enzymes contain a single site that participates in catalysis and nicotinamide regulation and provides additional insights into the Sir2 catalytic mechanism.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15780941}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15780941 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_15780941}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Sirt1]] | | [[Category: Sirt1]] |
| [[Category: Sirtuin]] | | [[Category: Sirtuin]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:08:20 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 09:19:39 2008'' |
