Structural and mechanistic insights into Mycothiol Disulphide Reductase and the Mycoredoxin-1-alkylhydroperoxide reductase E assembly of Mycobacterium tuberculosis

Biochimica Et Biophysica Acta. General Subjects
Arvind KumarGerhard Grüber

Abstract

Mycobacteria employ a versatile machinery of the mycothiol-dependent system, containing the proteins mycothiol disulfide reductase (Mtr), the oxido-reductase Mycoredoxin-1 (Mrx-1) and the alkyl-hydroperoxide subunit E (AhpE). The mycothiol-dependent protein ensemble regulates the balance of oxidized-reduced mycothiol, to ensure a reductive intracellular environment for optimal functioning of its proteins even upon exposure to oxidative stress. Here, we determined the first low-resolution solution structure of Mycobacterium tuberculosis Mtr (MtMtr) derived from small-angle X-ray scattering data, which provides insight into its dimeric state. The solution shape reveals the two NADPH-binding domains inside the dimeric MtMtr in different conformations. NMR-titration shows that the MtMtr-MtMrx-1 interaction is characterized by a fast exchange regime and critical residues involved in the protein-protein interaction were identified. Using NMR spectroscopy and docking studies, the epitopes of MtMrx-1 and MtAhpE interaction are described, shedding new light into the interaction interface and mechanism of action. Finally, the essential residue of MtMrx-1 identified in the interaction with MtMtr and MtAhpE form a platform for structure-gu...Continue Reading

Citations

May 24, 2018·American Journal of Reproductive Immunology : AJRI·Alicia R BerardAdam D Burgener
Jul 1, 2020·Antioxidants & Redox Signaling·Raffaella Bonavita, Mikko O Laukkanen
Feb 23, 2019·The Journal of Experimental Medicine·Lucía PiacenzaRafael Radi
Jul 18, 2019·The Journal of Biological Chemistry·Ernesto CuevasantaMadia Trujillo
Dec 31, 2020·FEMS Microbiology Ecology·Zachary J ButzChristopher J Ackerson

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