New insights on the molecular mechanism of action of human renalase

Renalase is a new human flavoprotein possibly involved in blood pressure and cardiac function regulation1. Despite the potential implications for human health, the biochemical properties of renalase have not been investigated so far, so that the molecular mechanism underlying its action is far from been understood. The low sequence identity with MAOs led to the hypothesis that renalase could represents a new class of monoamine oxidases, acting by degrading plasma catecholamines2,3. In order to elucidate the mechanism of action of human renalase at a molecular level, three recombinant forms of human renalase were produced in E. coli yielding amounts of protein suitable for its biochemical characterization4. Spectroscopic analyses revealed for the first time that renalase is a flavoprotein, with FAD as noncovalently-bound cofactor. At variance with MAOs, recombinant renalase was found to be devoid of any oxidase activity toward biogenic amines. Nevertheless, its unusual reactivity towards various compounds sheds a new light on the nature of the reaction catalyzed by this enzyme. 1. Xu J. et al. (2005) J. Clin. Invest. 115, 1275-1280 2. Li G. et al. (2008) Circulation 117, 1277-1282 3. Wang J. et al. (2008) Mol. Biol. Rep. 35, 613-620 4. Pandini V. et al. (2010) Protein Expr. Purif. 72, 244-53