Key result
Substitution of a single conserved deep binding pocket residue (V612) in E. coli AcrB alters its resistance phenotype and shifts the conformational equilibrium towards the tight state.
Why the study?
Antibiotic efflux by RND superfamily multidrug efflux pumps mediates multidrug resistance in Gram-negative bacteria, but the mechanisms of conformational plasticity and substrate specificity across phylogenetic clusters remain to be characterized.
Population
K. pneumoniae OqxB and E. coli AcrB multidrug efflux pumps
Comparison
Transfer of a single conserved residue between clusters vs parental/unmodified pumps
Design
In vitro structural and functional characterisation study
Authors
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Identifies two RND phylogenetic clusters with conserved residues; leaves open targeted inhibitor development against Gram-negative resistance.
Conformational heterogeneity between different RND clusters is phylogenetically conserved and influences substrate specificity and resistance phenotypes in Gram-negative bacteria.
Lazarova et al. (2024) studied Antibiotic resistance. V612 substitutions in AcrB vs. Wildtype AcrB was evaluated on Conformational states and substrate specificity. Substitution of a single conserved deep binding pocket residue (V612) in E. coli AcrB alters its resistance phenotype and shifts the conformational equilibrium towards the tight state.
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