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MANGANESE REDOX BIOCHEMISTRY

$225,049R01FY2000GMNIH

Oregon Graduate Institute Science &Tech, Beaverton OR

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Abstract

DESCRIPTION: (adapted from applicant's abstract) Manganese is a biologically important metal ion involved in catalysis, intracellular signalling, gene regulation, and metal homeostasis. Redox active Mn forms the active site of the antioxidant metalloenzymes, Mn superoxide dismutase and Mn catalase, which are involved in protection against the toxic oxygen metabolites, superoxide and hydrogen peroxide. These enzymes represent mononuclear and dinuclear structural motifs for Mn active sites and together illustrate most of the key features of Mn redox biochemistry, including multiple oxidation states, oxygen reactivity, and coupling to protons. The proposed research will probe the mechanisms of redox catalysis by E. coli Mn superoxide dismutase and lactobacillus plantarum Mn catalase using a combination of spectroscopic approaches, crystallography, and enzyme kinetics, mutagenically testing the function of specific elements of protein structure. These studies are expected to contribute fundamentally to the understanding of these two Mn redox metalloenzymes and provide new insights into manganese redox biochemistry

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