1s7g
From Proteopedia
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'''Structural Basis for the Mechanism and Regulation of Sir2 Enzymes''' | '''Structural Basis for the Mechanism and Regulation of Sir2 Enzymes''' | ||
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[[Category: Boeke, J D.]] | [[Category: Boeke, J D.]] | ||
[[Category: Wolberger, C.]] | [[Category: Wolberger, C.]] | ||
- | [[Category: | + | [[Category: Adp-ribose]] |
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- | [[Category: | + | [[Category: Sir2]] |
- | [[Category: | + | [[Category: Sirtuin]] |
- | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 08:23:30 2008'' | |
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Revision as of 05:23, 3 May 2008
Structural Basis for the Mechanism and Regulation of Sir2 Enzymes
Overview
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.
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 Page seeded by OCA on Sat May 3 08:23:30 2008
Categories: Archaeoglobus fulgidus | Single protein | Avalos, J L. | Boeke, J D. | Wolberger, C. | Adp-ribose | Enzyme | Nad+ | Sir2 | Sirtuin