4Y0L

Mycobacterial membrane protein MmpL11D2

Summary for 4Y0L

• Entry DOI: 10.2210/pdb4y0l/pdb
• Descriptor: Putative membrane protein mmpL11, IODIDE ION, SULFATE ION, ... (4 entities in total)
• Functional Keywords: rnd family, membrane protein
• Biological source: Mycobacterium tuberculosis
• Cellular location: Cell inner membrane ; Multi-pass membrane protein : P9WJT9
• Total number of polymer chains: 1
• Total formula weight: 10414.49

Authors

Torres, R.,Chim, N.,Goulding, C.W. (deposition date: 2015-02-06, release date: 2015-08-12, Last modification date: 2024-02-28)

Primary citation

Chim, N.,Torres, R.,Liu, Y.,Capri, J.,Batot, G.,Whitelegge, J.P.,Goulding, C.W.
The Structure and Interactions of Periplasmic Domains of Crucial MmpL Membrane Proteins from Mycobacterium tuberculosis.
Chem.Biol., 22:1098-1107, 2015

PubMed Abstract: Mycobacterium 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-Å 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.

PubMed: 26278184
DOI: 10.1016/j.chembiol.2015.07.013

Experimental method

X-RAY DIFFRACTION (2.4 Å)