Open AccessEvidence for the Dimerization-Mediated Catalysis of Methionine Sulfoxide Reductase A from Clostridium oremlandii
Author(s) -
Eun Hye Lee,
Kitaik Lee,
Geun Hee Kwak,
Yeon Seung Park,
Kong Joo Lee,
Kwang Yeon Hwang,
Hwa Young Kim
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0131523
Subject(s) - msra , chemistry , methionine sulfoxide reductase , dimer , sulfoxide , glutaredoxin , methionine sulfoxide , stereochemistry , methionine , catalysis , monomer , reductase , biochemistry , enzyme , amino acid , glutathione , organic chemistry , polymer
Clostridium oremlandii MsrA ( Co MsrA) is a natively selenocysteine-containing methionine-S-sulfoxide reductase and classified into a 1-Cys type MsrA. Co MsrA exists as a monomer in solution. Herein, we report evidence that Co MsrA can undergo homodimerization during catalysis. The monomeric Co MsrA dimerizes in the presence of its substrate methionine sulfoxide via an intermolecular disulfide bond between catalytic Cys16 residues. The dimeric Co MsrA 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 Co MsrA is confirmed. We also determine the crystal structure of the dimeric Co MsrA, 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 Co MsrA catalysis that is additionally involved in Co MsrA regeneration by glutaredoxin.