General Function

MnSOD is a homotetramer of 22 kDa subunits with one Mn³⁺ ion per monomer. MnSOD is found in mitochondria where it catalyzes the disproportionation of superoxide to O₂ and H₂O₂. MnSOD scavenges superoxide anions, the highly reactive oxygen species generated by univalent reduction of molecular oxygen during cellular respiration, O₂ radicals are damaging to cellular constituents because they attack proteins, nucleic acids and membrane lipids, thereby disrupting cellular function and integrity. The cumulative effect of this cellular damage contributes to many cellular pathologies, including mutagenesis, carcinogenesis, diabetes, neurodegenerative disease, inflammatory diseases, as well as to the overall process of cellular aging.

Catalysis

MnSOD catalyzes the dismutation of two molecules of superoxide anion into water and hydrogen peroxide. Catalysis by MnSOD has a rapid (10⁴ s^-1) proton transfer rate in catalysis. However, in contrast to carbonic anhydrase where several water molecules are utilized, the hydrogen bonded network involves up to five amino-acid side chains and two intervening water molecules. The proton transfer proceeds from the manganese-bound solvent (H₂O/OH^-, W1) through Q143, Y34, the second solvent molecule (W1) to H30 and finally to Y166 from an adjacent monomer.

Our Focus

Our lab has many projects in conjunction with the Silverman Lab that involves all aspects of MnSOD structure, catalysis, and function. We are interested in using various structural techniques (from X-ray crystallography, neutron diffraction to molecular modeling) to study the detailed structure of wild type, modified, and mutants forms MnSOD.

Selected Recent Publication

Quint, P, R. Reutzel, R. Mikulski, R. McKenna, D. N. Silverman. 2006. Structure and catalytic inhibition of nitrated human Mn superoxide dismutase: Mechanism of inactivation in conditions of oxidative stress. Free Radical Biology and Medicine, 40:453-458.
Quint 2006