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• W2507431544 abstract "The MmpL family of proteins translocates complex (glyco)lipids and siderophores across the cell envelope of mycobacteria and closely related Corynebacteriaceae and plays important roles in the biogenesis of the outer membrane of these organisms. Despite their significance in the physiology and virulence of Mycobacterium tuberculosis, and from the perspective of developing novel antituberculosis agents, little is known about their structure and mechanism of translocation. In this study, the essential mycobacterial mycolic acid transporter, MmpL3, and its orthologue in Corynebacterium glutamicum, CmpL1, were investigated as prototypical MmpL proteins to gain insight into the transmembrane topology, tertiary and quaternary structures, and functional regions of this transporter family. The combined genetic, biochemical, and biophysical studies indicate that MmpL3 and CmpL1 are structurally similar to Gram-negative resistance-nodulation and division efflux pumps. They harbor 12 transmembrane segments interrupted by two large soluble periplasmic domains and function as homotrimers to export long-chain (C22–C90) mycolic acids, possibly in their acetylated form, esterified to trehalose. The mapping of a number of functional residues within the middle region of the transmembrane domain of MmpL3 shows a striking overlap with mutations associated with resistance to MmpL3 inhibitors. The results suggest that structurally diverse inhibitors of MmpL3 all target the proton translocation path of the transporter and that multiresistance to these inhibitors is enabled by conformational changes in MmpL3." @default.
• W2507431544 created "2016-09-16" @default.
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• W2507431544 date "2016-09-01" @default.
• W2507431544 modified "2023-10-16" @default.
• W2507431544 title "Structure–Function Profile of MmpL3, the Essential Mycolic Acid Transporter from <i>Mycobacterium tuberculosis</i>" @default.
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• W2507431544 doi "https://doi.org/10.1021/acsinfecdis.6b00095" @default.
• W2507431544 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5117480" @default.
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• W2507431544 hasPublicationYear "2016" @default.
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