Targeting MmpL3 for anti-tuberculosis drug development
| Autor: | Bolla, Jani R. |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Tuberculosis
trehalose monomycolate Protein Conformation Biophysics Antitubercular Agents Computational biology Biology MmpL3 transporter Biochemistry Mycobacterium tuberculosis 03 medical and health sciences mode of action Bacterial Proteins Drug Development Structural Biology medicine Review Articles Lipid Transport 030304 developmental biology 0303 health sciences Molecular Interactions 030306 microbiology Pharmacology & Toxicology Membrane Transport Proteins Biological Transport biology.organism_classification medicine.disease Therapeutics & Molecular Medicine small molecule inhibitors Lipids Small molecule cell-wall biogenesis tuberculosis Mycolic Acids Membrane protein Drug development Biogenesis Function (biology) |
| Zdroj: | Biochemical Society Transactions |
| ISSN: | 1470-8752 0300-5127 |
| DOI: | 10.1042/bst20190950 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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