Targeting MmpL3 for anti-tuberculosis drug development | Zendy

Jani Reddy Bolla | Zendy

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Targeting MmpL3 for anti-tuberculosis drug development

Author(s) -

Jani Reddy Bolla

Publication year - 2020

Publication title -

biochemical society transactions

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.562

H-Index - 144

eISSN - 1470-8752

pISSN - 0300-5127

DOI - 10.1042/bst20190950

Subject(s) - biogenesis , lipid anchored protein , mycobacterium tuberculosis , cell envelope , biochemistry , biology , function (biology) , microbiology and biotechnology , chemistry , tuberculosis , gene , autophagy , medicine , apoptosis , pathology , escherichia coli

The unique architecture of the mycobacterial cell envelope plays an important role in Mycobacterium tuberculosis (Mtb) pathogenesis. A critical protein in cell envelope biogenesis in mycobacteria, required for transport of precursors, trehalose monomycolates (TMMs), is the Mycobacterial membrane protein large 3 (MmpL3). Due to its central role in TMM transport, MmpL3 has been an attractive therapeutic target and a key target for several preclinical agents. In 2019, the first crystal structures of the MmpL3 transporter and its complexes with lipids and inhibitors were reported. These structures revealed several unique structural features of MmpL3 and provided invaluable information on the mechanism of TMM transport. This review aims to highlight the recent advances made in the function of MmpL3 and summarises structural findings. The overall goal is to provide a mechanistic perspective of MmpL3-mediated lipid transport and inhibition, and to highlight the prospects for potential antituberculosis therapies.

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