Docking study with biological validation on bacterial enzyme MurD

Abstract

Abstract Approved antibiotics currently target only a small number of bacterial enzymes, despite increasing rates of antibiotic-resistant microbes. New chemical entities, especially with a novel mode of action, are ferociously being sought. To determine whether the ubiquitous bacterial enzyme Murein ligase D (MurD) could be inhibited in an alternative way to existing inhibitors, we performed molecular docking on a distinct site of the protein with potential new inhibitory properties. The compounds ranked highest by the docking program were acquired and screened for in vitro activity on isolated MurD. We found that the screened compounds exerted only marginal enzyme inhibitory activity, leading us to the conclusion that our hypothesis on a potential new binding site of MurD was too optimistic. We supplement this article with the names and structures of the screened molecules, to further assist is the search for novel antibiotic binding sites on Mur ligases.