A dual role of cysteine residues in the maturation of prokaryotic Cu/Zn-superoxide dismutase

Yoshiaki Furukawa, Atsuko Shintani, Teppei Kokubo

Research output: Contribution to journalArticlepeer-review

Abstract

Bacterial Cu/Zn-superoxide dismutase (SodC) is an enzyme catalyzing the disproportionation of superoxide radicals, to which the binding of copper and zinc ions and the formation of an intramolecular disulfide bond are essential. We previously showed that Escherichia coli SodC (SodC) was prone to spontaneous degradation in vivo in an immature form prior to the introduction of the disulfide bond. The post-translational maintenance involving the metal binding and the disulfide formation would thus control the stability as well as the enzymatic function of SodC; however, a mechanism of the SodC maturation remains obscure. Here, we show that the disulfide-reduced SodC can secure a copper ion as well as a zinc ion through the thiolate groups. Furthermore, the disulfide-reduced SodC was found to bind cuprous and cupric ions more tightly than SodC with the disulfide bond. The thiolate groups ligating the copper ion were then autooxidized to form the intramolecular disulfide bond, leading to the production of enzymatically active SodC. Based upon the experiments in vitro, therefore, we propose a mechanism for the activation of SodC, in which the conserved Cys residues play a dual role: the acquisition of a copper ion for the enzymatic activity and the formation of the disulfide bond for the structural stabilization.

Original languageEnglish
JournalMetallomics
Volume13
Issue number9
DOIs
Publication statusPublished - 2021 Sep 2

Keywords

  • copper
  • disulfide
  • protein folding
  • superoxide dismutase (SOD)
  • zinc

ASJC Scopus subject areas

  • Chemistry (miscellaneous)
  • Biophysics
  • Biochemistry
  • Biomaterials
  • Metals and Alloys

Fingerprint

Dive into the research topics of 'A dual role of cysteine residues in the maturation of prokaryotic Cu/Zn-superoxide dismutase'. Together they form a unique fingerprint.

Cite this