title: Bacterial mechanisms of reversible protein S-thiolation: structural and mechanistic insights into mycoredoxins.
abstract: Mycobacteria produce millimolar concentrations of mycothiol (MSH) as their major low molecular weight thiol redox buffer. MSH-deficient mutants display increased sensitivity towards reactive oxygen, nitrogen and electrophilic species as well as alkylating agents and antibiotics. MSH is maintained in its reduced thiol state by the NADPH-dependent mycothiol disulphide reductase (Mtr). However, the redoxin that uses the MSH/Mtr/NADPH pathway for reduction of MSH-mixed protein disulphides, formed during oxidative stress, has long remained unknown. In this issue, Van Laer et al. report that MSH provides the reducing power for mycoredoxin-1 (Mrx1) in reduction of synthetic MSH-mixed disulphides. The reduced (dithiol) and oxidized (disulphide) solution structures of Mrx1 have been solved by nuclear magnetic resonance (NMR) spectroscopy. NMR time course experiments have also demonstrated the transient S-mycothiolation of the active site Cys14 of oxidized Mrx1 during reduction by the MSH/Mtr/NADPH electron pathway. The paper opens a new era of research to identify S-mycothiolated Mrx1 substrates and the function of MSH in redox regulation and virulence in Mycobacterium tuberculosis.
authors.affiliation: Institute for Microbiology, Ernst-Moritz-Arndt-University of Greifswald, D-17487, Greifswald, Germany. antelman@uni-greifswald.de
authors.forename: Haike
authors.initials: H
authors.lastname: Antelmann
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Hamilton
mesh_terms: D003545:Cysteine / Q000378:metabolism*; D006020:Glycopeptides / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism*; D020102:Mycobacterium smegmatis / Q000201:enzymology* / Q000502:physiology*; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000378:metabolism*
chemical_list: D006020:Glycopeptides; C089265:mycothiol; D007294:Inositol; D010088:Oxidoreductases; D003545:Cysteine