Molecular Rationale behind the Differential Substrate Specificity of Bacterial RND Multi-Drug Transporters.

ABSTRACT: Resistance-Nodulation-cell Division (RND) transporters AcrB and AcrD of Escherichia coli expel a wide range of substrates out of the cell in conjunction with AcrA and TolC, contributing to the onset of bacterial multidrug resistance. Despite sharing an overall sequence identity of ~66% (similarity ~80%), these RND transporters feature distinct substrate specificity patterns whose underlying basis remains elusive. We performed exhaustive comparative analyses of the putative substrate binding pockets considering crystal structures, homology models and conformations extracted from multi-copy μs-long molecular dynamics simulations of both AcrB and AcrD. The impact of physicochemical and topographical properties (volume, shape, lipophilicity, electrostatic potential, hydration and distribution

SUBMITTER: Ramaswamy VK 

PROVIDER: S-EPMC5556075 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature