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Additional file 7: Figure S6. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance

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posted on 2016-03-23, 05:00 authored by Jody Phelan, Francesc Coll, Ruth McNerney, David Ascher, Douglas Pires, Nick Furnham, Nele Coeck, Grant Hill-Cawthorne, Mridul Nair, Kim Mallard, Andrew Ramsay, Susana Campino, Martin Hibberd, Arnab Pain, Leen Rigouts, Taane Clark
Molecular interactions established by wild-type residues in katG and rpoB residues. (A) The interactions established by Ser315 in katG. Given the proximity of the residue to the ligands INH and HEM, mutations to Asn and Thr, with slightly larger side chains, would potentially cause steric clashes. (B) The interactions of Asp435 in rpoB. It directly interacts with RMP via polar interactions that would be disrupted by mutations to Val. (C) Thr400 in rpoB is at the end of an alpha helix establishing intra molecular interactions. Giving its distance to RMP, it would be expected that its mutation to Ala would be a lower impact, which would arise from alosteric changes. (D) Ser450 establishes strong intra molecular interactions in the RMP binding site. Mutations to larger residues (Trp and Leu) could disrupt the packing of the region and therefore binding. (E). Ile491 performs hydrophobic interactions with RMP and its neighbouring residues. Mutations to Phe or Val would compromise packing, either inducing steric clashes or compromising packing. (F). His445 performs strong intra molecular interactions, including a donor-pi (blue dashes) and hydrogen bond (red dashes). Mutations to residues Asp, Tyr or Arg would imply in the loss of the pi interaction as well as potential introduction of steric clashes. (PNG 749 kb)

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