Structural analysis of 1-Cys type selenoprotein methionine sulfoxide reductase A

Eun Hye Lee, Geun Hee Kwak, Moon Jung Kim, Hwa Young Kim, Kwang Yeon Hwang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Methionine sulfoxide reductase A (MsrA) reduces free and protein-based methionine-S-sulfoxide to methionine. Structures of 1-Cys MsrAs lacking a resolving Cys, which interacts with catalytic Cys, are unknown. In addition, no structural information on selenocysteine (Sec)-containing MsrA enzymes has been reported. In this work, we determined the crystal structures of 1-Cys type selenoprotein MsrA from Clostridium oremlandii at 1.6-1.8 Å, including the reduced, oxidized (sulfenic acid), and substrate-bound forms. The overall structure of Clostridium MsrA, consisting of ten α-helices and six β-strands, folds into a catalytic domain and a novel helical domain absent from other known MsrA structures. The helical domain, containing five helices, tightly interacts with the catalytic domain, and is likely critical for catalytic activity due to its association with organizing the active site. This helical domain is also conserved in several selenoprotein MsrAs. Our structural analysis reveals that the side chain length of Glu55 is critical for the proton donor function of this residue. Our structures also provide insights into the architecture of the 1-Cys MsrA active site and the roles of active site residues in substrate recognition and catalysis.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume545
DOIs
Publication statusPublished - 2014 Mar 1

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Methionine Sulfoxide Reductases
Selenoproteins
Structural analysis
Catalytic Domain
Clostridium
sulfoxide
Methionine
Sulfenic Acids
Selenocysteine
Substrates
Catalysis
Chain length
Protons
Catalyst activity
Crystal structure
Association reactions
Enzymes

Keywords

  • Catalysis
  • Clostridium
  • Methionine sulfoxide reductase
  • MsrA
  • Selenocysteine
  • Selenoprotein

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Structural analysis of 1-Cys type selenoprotein methionine sulfoxide reductase A. / Lee, Eun Hye; Kwak, Geun Hee; Kim, Moon Jung; Kim, Hwa Young; Hwang, Kwang Yeon.

In: Archives of Biochemistry and Biophysics, Vol. 545, 01.03.2014, p. 1-8.

Research output: Contribution to journalArticle

Lee, Eun Hye ; Kwak, Geun Hee ; Kim, Moon Jung ; Kim, Hwa Young ; Hwang, Kwang Yeon. / Structural analysis of 1-Cys type selenoprotein methionine sulfoxide reductase A. In: Archives of Biochemistry and Biophysics. 2014 ; Vol. 545. pp. 1-8.
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N2 - Methionine sulfoxide reductase A (MsrA) reduces free and protein-based methionine-S-sulfoxide to methionine. Structures of 1-Cys MsrAs lacking a resolving Cys, which interacts with catalytic Cys, are unknown. In addition, no structural information on selenocysteine (Sec)-containing MsrA enzymes has been reported. In this work, we determined the crystal structures of 1-Cys type selenoprotein MsrA from Clostridium oremlandii at 1.6-1.8 Å, including the reduced, oxidized (sulfenic acid), and substrate-bound forms. The overall structure of Clostridium MsrA, consisting of ten α-helices and six β-strands, folds into a catalytic domain and a novel helical domain absent from other known MsrA structures. The helical domain, containing five helices, tightly interacts with the catalytic domain, and is likely critical for catalytic activity due to its association with organizing the active site. This helical domain is also conserved in several selenoprotein MsrAs. Our structural analysis reveals that the side chain length of Glu55 is critical for the proton donor function of this residue. Our structures also provide insights into the architecture of the 1-Cys MsrA active site and the roles of active site residues in substrate recognition and catalysis.

AB - Methionine sulfoxide reductase A (MsrA) reduces free and protein-based methionine-S-sulfoxide to methionine. Structures of 1-Cys MsrAs lacking a resolving Cys, which interacts with catalytic Cys, are unknown. In addition, no structural information on selenocysteine (Sec)-containing MsrA enzymes has been reported. In this work, we determined the crystal structures of 1-Cys type selenoprotein MsrA from Clostridium oremlandii at 1.6-1.8 Å, including the reduced, oxidized (sulfenic acid), and substrate-bound forms. The overall structure of Clostridium MsrA, consisting of ten α-helices and six β-strands, folds into a catalytic domain and a novel helical domain absent from other known MsrA structures. The helical domain, containing five helices, tightly interacts with the catalytic domain, and is likely critical for catalytic activity due to its association with organizing the active site. This helical domain is also conserved in several selenoprotein MsrAs. Our structural analysis reveals that the side chain length of Glu55 is critical for the proton donor function of this residue. Our structures also provide insights into the architecture of the 1-Cys MsrA active site and the roles of active site residues in substrate recognition and catalysis.

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