1s7g

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spinqualitylabelsall models 1s7g, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 with ZN, SO4, NAD, APR, 2PE, P6G, PG4, 1PE and EDO as ligands. 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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