4zzl

MexR R21W derepressor mutant causing multidrug resistance in P. aeruginosa by mexAB-oprM efflux pump expression

spinqualitylabelsall models 4zzl, resolution 2.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4zzl is a 2 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.19Å Ligands: GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MEXR_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 PubMed MexR 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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