Sensing NAD metabolites through macro domains

Front Biosci (Landmark Ed). 2009 Jan 1;14:3246-58. doi: 10.2741/3448.


The macro module is a globular protein domain of about 25 kDa that is evolutionarily conserved in organisms from viruses, bacteria, yeast to humans. It is generally part of proteins that have wide-ranging (and yet to be discovered) cellular functions. There are several examples of macro domains associated with modules showing homology to poly-ADP-ribosyl-polymerases. Many macro domains, including those of the human histone macroH2A1.1, bind NAD metabolites such as ADP-ribose, suggesting that macro domains may function in the recognition of this and related molecules. The presence of a metabolite-binding function in a repressive chromatin component opens new potential connections between chromosome structure, gene silencing and cellular metabolism. Current evidence suggests that macro domains also represent a novel tool for studying NAD metabolites and may be an attractive drug target for the treatment of diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bacteria / metabolism
  • Histones / metabolism
  • NAD / metabolism*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Viruses / metabolism


  • Histones
  • NAD
  • Poly(ADP-ribose) Polymerases