Structural insights into a bifunctional peptide methionine sulfoxide reductase msra/b fusion protein from helicobacter pylori

Sulhee Kim, Kitaik Lee, Sun Ha Park, Geun Hee Kwak, Min Seok Kim, Hwa Young Kim, Kwang Yeon Hwang

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Methionine sulfoxide reductase (Msr) is a family of enzymes that reduces oxidized methi-onine and plays an important role in the survival of bacteria under oxidative stress conditions. MsrA and MsrB exist in a fusion protein form (MsrAB) in some pathogenic bacteria, such as Helicobacter pylori (Hp), Streptococcus pneumoniae, and Treponema denticola. To understand the fused form instead of the separated enzyme at the molecular level, we determined the crystal structure of HpMsrABC44S/C318S at 2.2 Å, which showed that a linker region (Hpiloop, 193–205) between two do-mains interacted with each HpMsrA or HpMsrB domain via three salt bridges (E193-K107, D197-R103, and K200-D339). Two acetate molecules in the active site pocket showed an sp2 planar electron density map in the crystal structure, which interacted with the conserved residues in fusion MsrABs from the pathogen. Biochemical and kinetic analyses revealed that Hpiloop is required to increase the catalytic efficiency of HpMsrAB. Two salt bridge mutants (D193A and E199A) were located at the entrance or tailgate of Hpiloop. Therefore, the linker region of the MsrAB fusion enzyme plays a key role in the structural stability and catalytic efficiency and provides a better understanding of why MsrAB exists in a fused form.

Original languageEnglish
Article number389
Pages (from-to)1-13
Number of pages13
JournalAntioxidants
Volume10
Issue number3
DOIs
Publication statusPublished - 2021 Mar

Keywords

  • Catalytic efficiency
  • Fusion protein
  • Linker region
  • MsrAB

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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