Evidence for the Dimerization-Mediated Catalysis of Methionine Sulfoxide Reductase A from Clostridium oremlandii
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| Authors: | Eun Hye Lee Kitaik Lee Geun-Hee Kwak Yeon Seung Park Kong-Joo Lee Kwang Yeon Hwang Hwa-Young Kim |
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| Institution: | 1. Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136–701, Republic of Korea.; 2. Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, Daegu 705–717, Republic of Korea.; 3. Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120–750, Republic of Korea.; University of Alberta, CANADA, |
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| Abstract: | Clostridium oremlandii MsrA (CoMsrA) is a natively selenocysteine-containing methionine-S-sulfoxide reductase and classified into a 1-Cys type MsrA. CoMsrA exists as a monomer in solution. Herein, we report evidence that CoMsrA can undergo homodimerization during catalysis. The monomeric CoMsrA dimerizes in the presence of its substrate methionine sulfoxide via an intermolecular disulfide bond between catalytic Cys16 residues. The dimeric CoMsrA is resolved by the reductant glutaredoxin, suggesting the relevance of dimerization in catalysis. The dimerization reaction occurs in a concentration- and time-dependent manner. In addition, the occurrence of homodimer formation in the native selenoprotein CoMsrA is confirmed. We also determine the crystal structure of the dimeric CoMsrA, having the dimer interface around the two catalytic Cys16 residues. A central cone-shaped hole is present in the surface model of dimeric structure, and the two Cys16 residues constitute the base of the hole. Collectively, our biochemical and structural analyses suggest a novel dimerization-mediated mechanism for CoMsrA catalysis that is additionally involved in CoMsrA regeneration by glutaredoxin. |
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