Structural highlights
FunctionMEXR_PSEAE Repressor of the mexAB-oprM multidrug resistance operon. Also represses its own expression. Many variants lead to increased expression of the mexAB-oprM operon. Publication Abstract from PubMedMexR is a repressor of the MexAB-OprM multidrug efflux pump operon of Pseudomonas aeruginosa, where DNA-binding impairing mutations lead to multidrug resistance (MDR). Surprisingly, the crystal structure of an MDR-conferring MexR mutant R21W (2.19 A) presented here is closely similar to wild-type MexR. However, our extended analysis, by molecular dynamics and small-angle X-ray scattering, reveals that the mutation stabilizes a ground state that is deficient of DNA binding and is shared by both mutant and wild-type MexR, whereas the DNA-binding state is only transiently reached by the more flexible wild-type MexR. This population shift in the conformational ensemble is effected by mutation-induced allosteric coupling of contact networks that are independent in the wild-type protein. We propose that the MexR-R21W mutant mimics derepression by small-molecule binding to MarR proteins, and that the described allosteric model based on population shifts may also apply to other MarR family members. Mutation-Induced Population Shift in the MexR Conformational Ensemble Disengages DNA Binding: A Novel Mechanism for MarR Family Derepression.,Anandapadamanaban M, Pilstal R, Andresen C, Trewhella J, Moche M, Wallner B, Sunnerhagen M Structure. 2016 Jul 13. pii: S0969-2126(16)30133-2. doi:, 10.1016/j.str.2016.06.008. PMID:27427478[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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