Substrate-induced structural alterations of Mycobacterial mycothione reductase and critical residues involved

• Main Authors: Kumar, Arvind, Subramanian Manimekalai, Malathy Sony, Grüber, Gerhard
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2020
• Subjects: Science::Biological sciences; Mycothiol; Oxidative Stress
• Online Access: https://hdl.handle.net/10356/145102
• Institution: Nanyang Technological University

Redox homeostasis is a prerequisite for survival of the pathogen Mycobacterium tuberculosis (Mtb) which employs the low molecular weight thiol mycothiol (MSH). The Mycobacterial NADPH-dependent mycothione reductase (MtMtr), composed of an NADPH-, FAD-, and a dimerization-domain connected by linkers, regulates the balance of oxidized-reduced MSH. Here, we demonstrate by small-angle X-ray scattering, that NADPH-binding alters the oligomeric state equilibrium of the protein with no significant overall structural change after MSH-binding. Mutation of critical residues in the linker regions of MtMtr eliminate partially or totally the NADPH-induced oligomerization effect with simultaneous effect on enzyme activity. The data provide insight into the MtMtr linker regions involved in the novel oligomerization equilibrium of the Mycobacterial enzyme.