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Marletta wins 2007 Repligen Award in Chemistry of Biological Processes


Michael Marletta, Chair of the Department of Chemistry, has won the American Chemical Society’s 2007 Repligen Award in Chemistry of Biological Processes.

The award recognizes Marletta's demonstration that nitric oxide is an intermediate in the formation of nitrite and nitrate in macrophages. The award also recognizes his characterization of the mechanism for the formation of NO from arginine catalyzed by nitric oxide synthase, and his elucidation of the mechanism for the regulation of quanylate cyclase by nitric oxide. This work places Marletta in the forefront of the world's finest mechanistic biochemists.

Few investigators in 1985 knew anything about nitric oxide, and none anticipated that this gas arose in mammalian systems from the amino acid arginine. In that year Marletta demonstrated that mouse macrophages produce nitrite and nitrate, and this led to the discovery of nitric oxide in mammals. The detection of nitric oxide caused Marletta to turn his attention to unraveling the biosynthetic pathway for its formation.

He showed that arginine is the precursor to nitric oxide and that a single enzyme, nitric oxidesynthase (NOS), converts arginine to citrulline and nitric oxide. Marletta and coworkers expressed the gene for nitric oxide synthase from macrophages in baculovirus. Their studies on the mechanism of enzyme action showed that NOS was a heme protein with a heme reductase domain, and that the enzyme also uses flavin and pterin cofactors.

Marletta has investigated a functionally diverse set of guanylate cyclase-like heme domains. Some of these domains have been found to use O2 as a signaling reagent. Marletta and coworkers have characterized the relationship between these domains by determining the structural changes that convert a guanylate cyclase-like heme domain from an NO to an O2 sensor. This domain now serves as paradigm for signaling with NO, O2 and perhaps CO.

Marletta's discoveries have led to an explosion in the field of NO research. According to the ACS announcement, “His intellectual creativity and bold experimental outlook will continue to direct his research program to study challenging and medically important problems at the forefront of biological chemistry.”

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