10.5452/MA-I5X0F
Ramaswamy, Venkata Krishnan; Vargiu, Attilio Vittorio; Malloci, Giuliano; Dreier, Jürg; Ruggerone, Paolo
Multidrug transporter AcrD of E. coli
modelarchive.org
2020
3D macromolecular model
2020-03-12
en
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. AcrB is the best characterized RND transporter, and its structure has been solved by several labs both without and with bound substrates and inhibitors. AcrD, a close homolog of AcrB, shares an overall sequence identity of nearly 66% (similarity ~80%) but features distinct substrate specificity pattern whose underlying basis remains elusive. This void of knowledge traces back mainly to the lack of experimental structures of AcrD and of co-crystal structures of any RND transporter with compounds belonging to beta-lactam, fluoroquinolone or aminoglycoside classes. Here, we present a thoroughly validated AcrD structure generated by template-based homology modelling using the high-resolution crystal structure of AcrB (PDB ID: 4DX5, 1.9 Å) as the template. The model was built using Modeller 9.13 and subjected to various geometric and stereochemical quality factors to evaluate backbone angles, side chain flips, rotamers, steric clashes etc. using state-of-the-art bioinformatics tools. The stability of the AcrD model, as well as its suitability for subsequent analyses, were validated in two independent μs-long MD simulations.