1s7g

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{{STRUCTURE_1s7g| PDB=1s7g | SCENE= }}
{{STRUCTURE_1s7g| PDB=1s7g | SCENE= }}
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'''Structural Basis for the Mechanism and Regulation of Sir2 Enzymes'''
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===Structural Basis for the Mechanism and Regulation of Sir2 Enzymes===
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==Overview==
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Sir2 proteins form a family of NAD(+)-dependent protein deacetylases required for diverse biological processes, including transcriptional silencing, suppression of rDNA recombination, control of p53 activity, regulation of acetyl-CoA synthetase, and aging. Although structures of Sir2 enzymes in the presence and absence of peptide substrate or NAD(+) have been determined, the role of the enzyme in the mechanism of deacetylation and NAD(+) cleavage is still unclear. Here, we present additional structures of Sir2Af2 in several differently complexed states: in a productive complex with NAD(+), in a nonproductive NAD(+) complex with bound ADP-ribose, and in the unliganded state. We observe a new mode of NAD(+) binding that seems to depend on acetyl-lysine binding, in which the nicotinamide ring of NAD(+) is buried in the highly conserved "C" pocket of the enzyme. We propose a detailed structure-based mechanism for deacetylation and nicotinamide inhibition of Sir2 consistent with mutagenesis and enzymatic studies.
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(as it appears on PubMed at http://www.pubmed.gov), where 15023335 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15023335}}
==About this Structure==
==About this Structure==
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[[Category: Sir2]]
[[Category: Sir2]]
[[Category: Sirtuin]]
[[Category: Sirtuin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 08:23:30 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 23:17:33 2008''

Revision as of 20:17, 27 July 2008

Image:1s7g.png

Template:STRUCTURE 1s7g

Structural Basis for the Mechanism and Regulation of Sir2 Enzymes

Template:ABSTRACT PUBMED 15023335

About this Structure

1S7G is a Single protein structure of sequence from Archaeoglobus fulgidus. Full crystallographic information is available from OCA.

Reference

Structural basis for the mechanism and regulation of Sir2 enzymes., Avalos JL, Boeke JD, Wolberger C, Mol Cell. 2004 Mar 12;13(5):639-48. PMID:15023335

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