NAD as a signaling molecule: ADP-ribosyltransferases
ADP-ribosyl-transferases participate in signaling pathways in bacteria, yeast, plants and humans and use NAD as a non-redox electrophile to accomplish post-translational modification of proteins or second messenger formation. Specific biological effects traced to the ADP-ribosyl-transferases include lifespan regulation, metabolic control, adaptation to environmental stress, genome stability (recombination), transcriptional silencing, heterochromatin formation and maintenance, DNA repair and calcium signaling. Enzymes of interest to the laboratory include the recently discovered Sir2 NAD dependent deacetylases, the ADP-ribosyl-cyclases including human CD38, and the poly-ADP-ribosylpolymerases (PARPs). Work in my laboratory explores 1. the biochemical principles of NAD activation, biochemical reaction mechanisms, and the regulation of enzyme activity, 2. the design and synthesis of small molecules that can either activate or inhibit these enzymes and the development of small molecule tools for the study of these enzymes in vivo.
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