Bacterial mechanisms of reversible protein S-thiolation: structural and mechanistic insights into mycoredoxins

Antelmann, Haike and Hamilton, Chris J. (2012) Bacterial mechanisms of reversible protein S-thiolation: structural and mechanistic insights into mycoredoxins. Molecular Microbiology, 86 (4). pp. 759-764. ISSN 1365-2958

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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.

Item Type:	Article
Additional Information:	Funding information: Deutsche Forschungsgemeinschaft. Grant Numbers: AN746/2-1, AN746/3-1; Biotechnology and Biological Science Research Council. Grant Number: BB/H013504/1; Leverhulme Trust. Grant Number: RPG-2012-606
Faculty \ School:	Faculty of Science > School of Pharmacy (former - to 2024)
UEA Research Groups:	Faculty of Science > Research Groups > Chemical Biology and Medicinal Chemistry (former - to 2021) Faculty of Science > Research Groups > Medicinal Chemistry (former - to 2017)
Depositing User:	Users 2731 not found.
Date Deposited:	03 Oct 2012 10:15
Last Modified:	22 Jul 2024 14:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/39746
DOI:	10.1111/mmi.12031

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