4y0l
From Proteopedia
Mycobacterial membrane protein MmpL11D2
Structural highlights
Function[MMPLB_MYCTU] Part of a heme-iron acquisition system. Receives heme from the heme-binding protein Rv0203 and transports it into the mycobacterial cell. Contributes to virulence.[1] [2] [3] Could also transport the mycolic acid-containing lipids monomeromycolyl diacylglycerol (MMDAG) and mycolate ester wax (WE) to the bacterial surface.[4] Publication Abstract from PubMedMycobacterium tuberculosis mycobacterial membrane protein large (MmpL) proteins are important in substrate transport across the inner membrane. Here, we show that MmpL proteins are classified into two phylogenetic clusters, where MmpL cluster II contains three soluble domains (D1, D2, and D3) and has two full-length members, MmpL3 and MmpL11. Significantly, MmpL3 is currently the most druggable M. tuberculosis target. We have solved the 2.4-A MmpL11-D2 crystal structure, revealing structural homology to periplasmic porter subdomains of RND (multidrug) transporters. The resulting predicted cluster II MmpL membrane topology has D1 and D2 residing, and possibly interacting, within the periplasm. Crosslinking and biolayer interferometry experiments confirm that cluster II D1 and D2 bind with weak affinities, and guided D1-D2 heterodimeric model assemblies. The predicted full-length MmpL3 and MmpL11 structural models reveal key substrate binding and transport residues, and may serve as templates to set the stage for in silico anti-tuberculosis drug development. The Structure and Interactions of Periplasmic Domains of Crucial MmpL Membrane Proteins from Mycobacterium tuberculosis.,Chim N, Torres R, Liu Y, Capri J, Batot G, Whitelegge JP, Goulding CW Chem Biol. 2015 Aug 20;22(8):1098-107. doi: 10.1016/j.chembiol.2015.07.013. Epub , 2015 Aug 13. PMID:26278184[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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