Structural highlights
FunctionPublication Abstract from PubMedMycothiol S-transferase (MST) (encoded by the rv0443 gene) was previously identified as the enzyme responsible for the transfer of Mycothiol (MSH) to xenobiotic acceptors in Mycobacterium tuberculosis (M.tb) during xenobiotic stress. To further characterize the functionality of MST in vitro and the possible roles in vivo, X-ray crystallographic, metal-dependent enzyme kinetics, thermal denaturation studies, and antibiotic MIC determination in rv0433 knockout strain were performed. The binding of MSH and Zn(2+) increases the melting temperature by 12.9 degrees C as a consequence of the cooperative stabilization of MST by both MSH and metal. The co-crystal structure of MST in complex with MSH and Zn(2+) to 1.45 A resolution supports the specific utilization of MSH as a substrate as well as affording insights into the structural requirements of MSH binding and the metal-assisted catalytic mechanism of MST. Contrary to the well-defined role of MSH in mycobacterial xenobiotic responses and the ability of MST to bind MSH, cell-based studies with an M.tb rv0443 knockout strain failed to provide evidence for a role of MST in processing of rifampicin or isoniazid. These studies suggest the necessity of a new direction to identify acceptors of the enzyme and better define the biological role of MST in mycobacteria. The Mycobacterium tuberculosis mycothiol S-transferase is divalent metal-dependent for mycothiol binding and transfer.,Jayasinghe YP, Banco MT, Lindenberger JJ, Favrot L, Palcekova Z, Jackson M, Manabe S, Ronning DR RSC Med Chem. 2023 Jan 26;14(3):491-500. doi: 10.1039/d2md00401a. eCollection , 2023 Mar 22. PMID:36970142[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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