2OD2: Crystal Structure Of Yhst2 I117f Mutant Bound To Carba-nad+ And An Acetylated H4 Peptide

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.
PDB ID: 2OD2Download
MMDB ID: 44687
PDB Deposition Date: 2006/12/21
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Saccharomyces cerevisiae
Similar Structures:
Biological Unit for 2OD2: dimeric; determined by author and by software (PISA)
Molecular Components in 2OD2
Label Count Molecule
Proteins (2 molecules)
Nad-dependent Deacetylase Hst2(Gene symbol: HST2)
Molecule annotation
Acetylated H4 Peptide
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB