title: Evidence for the dimerization-mediated catalysis of methionine sulfoxide reductase A from Clostridium oremlandii.
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.
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Lee
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Kitaik
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, Daegu 705-717, Republic of Korea.
authors.forename: Geun-Hee
authors.initials: GH
authors.lastname: Kwak
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Yeon Seung
authors.initials: YS
authors.lastname: Park
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Kong-Joo
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Kwang Yeon
authors.initials: KY
authors.lastname: Hwang
authors.affiliation: Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, Daegu 705-717, Republic of Korea.
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Kim
mesh_terms: D000465:Algorithms; D002384:Catalysis; D003013:Clostridium / Q000201:enzymology*; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry; D054477:Glutaredoxins / Q000737:chemistry; D013058:Mass Spectrometry; D051150:Methionine Sulfoxide Reductases / Q000378:metabolism*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D055503:Protein Multimerization; D017279:Selenocysteine / Q000378:metabolism; D051140:Selenoproteins / Q000378:metabolism
chemical_list: D004220:Disulfides; D054477:Glutaredoxins; D051140:Selenoproteins; D017279:Selenocysteine; D051150:Methionine Sulfoxide Reductases