4y1k
PALMITOYLATED OPRM OUTER MEMBRANE FACTOR
Structural highlights
FunctionOPRM_PSEAE The outer membrane component of the MexAB-OprM efflux system that confers multidrug resistance. Also functions as the major efflux pump for n-hexane and p-xylene efflux. Over-expression of the pump increases antibiotic and solvent efflux capacities. Can replace the OprJ outer membrane component of the MexCD-OprJ pump; the antibiotics exported are those exported by the intact MexCD pump, showing that efflux substrate specificity is not conferred by this component. Serves as the outer membrane component for the MexXY efflux system. Implicated in the secretion of the siderophore pyoverdine. OprM is probably involved in the efflux of the siderophore across the outer membrane.[1] [2] [3] [4] [5] The ability to export antibiotics and solvents is dramatically decreased in the presence of the proton conductor carbonyl cyanide m-chlorophenylhydrazone (CCCP), showing that an energized inner membrane is required for efflux. It is thought that the MexB subunit is a proton antiporter.[6] [7] [8] [9] [10] Publication Abstract from PubMedAmong the different mechanisms used by bacteria to resist antibiotics, active e ffl ux plays a major role. In Gram-negative bacteria, active e ffl ux is carried out by tripartite e ffl ux pumps that form a macromolecular assembly spanning both membranes of the cellular wall. At the outer membrane level, a well-conserved outer membrane factor (OMF) protein acts as an exit duct, but its sequence varies greatly among different species. The OMFs share a similar tri-dimensional structure that includes a beta-barrel pore domain that stabilizes the channel within the membrane. In addition, OMFs are often subjected to different N-terminal post-translational modifications (PTMs), such as an acylation with a lipid. The role of additional N-terminal anchors is all the more intriguing since it is not always required among the OMFs family. Understanding this optional PTM could open new research lines in the field of antibiotics resistance. In Escherichia coli, it has been shown that CusC is modified with a tri-acylated lipid, whereas TolC does not show any modification. In the case of OprM from Pseudomonas aeruginosa, the N-terminal modification remains a matter of debate, therefore, we used several approaches to investigate this issue. As definitive evidence, we present a new X-ray structure at 3.8 A resolution that was solved in a new space group, making it possible to model the N-terminal residue as a palmitoylated cysteine. New OprM structure highlighting the nature of the N-terminal anchor.,Monlezun L, Phan G, Benabdelhak H, Lascombe MB, Enguene VY, Picard M, Broutin I Front Microbiol. 2015 Jul 1;6:667. doi: 10.3389/fmicb.2015.00667. eCollection, 2015. PMID:26191054[11] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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