2OD2

Crystal Structure of yHst2 I117F mutant bound to carba-NAD+ and an acetylated H4 peptide

Summary for 2OD2

• Entry DOI: 10.2210/pdb2od2/pdb
• Related: 1SZC 1SZD 2OD7 2OD9
• Descriptor: NAD-dependent deacetylase HST2, Acetylated H4 peptide, ZINC ION, ... (6 entities in total)
• Functional Keywords: zn binding protein, rossmann fold, hydrolase
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Cellular location: Cytoplasm: P53686
• Total number of polymer chains: 2
• Total formula weight: 37536.01

Authors

Sanders, B.D. (deposition date: 2006-12-21, release date: 2007-02-20, Last modification date: 2024-10-30)

Primary citation

Sanders, B.D.,Zhao, K.,Slama, J.T.,Marmorstein, R.
Structural basis for nicotinamide inhibition and base exchange in sir2 enzymes.
Mol.Cell, 25:463-472, 2007

PubMed Abstract: The Sir2 family of proteins consists of broadly conserved NAD(+)-dependent deacetylases that are implicated in diverse biological processes, including DNA regulation, metabolism, and longevity. Sir2 proteins are regulated in part by the cellular concentrations of a noncompetitive inhibitor, nicotinamide, that reacts with a Sir2 reaction intermediate via a base-exchange reaction to reform NAD(+) at the expense of deacetylation. To gain a mechanistic understanding of nicotinamide inhibition in Sir2 enzymes, we captured the structure of nicotinamide bound to a Sir2 homolog, yeast Hst2, in complex with its acetyl-lysine 16 histone H4 substrate and a reaction intermediate analog, ADP-HPD. Together with related biochemical studies and structures, we identify a nicotinamide inhibition and base-exchange site that is distinct from the so-called "C pocket" binding site for the nicotinamide group of NAD(+). These results provide insights into the Sir2 mechanism of nicotinamide inhibition and have important implications for the development of Sir2-specific effectors.

PubMed: 17289592
DOI: 10.1016/j.molcel.2006.12.022

Experimental method

X-RAY DIFFRACTION (2 Å)