Overview

The Mur ligases are a set of four Mur ubiquitin ligase enzymes: MurC, MurD, MurE, and MurF which catalyze the addition of a short polypeptide to UDP-D-acetylmuramic acid in the process of bacterial cell wall buildup from peptidoglycans. The four enzymes catalyze sequential ATP‐dependent ligations to the growing peptide chain of the developing peptidoglycan unit.

Many of the most effective antibiotics target fundamental pathways such as, bacterial cell wall biosynthesis, DNA replication and protein biosynthesis. The Mur Ligase enzymes are excellent antibacterial targets because they are essential for bacterial survival, and the enzymes are conserved across a number of important bacteria. In addition they are absent in eukaryotes (see PubMed link and PubMed link).

Our OSA project (pre-publication) and Mur ligase targets were under-referenced in 2023. See Nature Reviews Link

Our goal is to develop a small-molecule inhibitor of two or more bacterial Mur ligases. We are pursuing three different approaches to achieve this:

1. Fragment screening and elaboration
2. Modification of existing inhibitors
3. De novo compound design (Atomwise collaboration)

More information about each project may be found in the relevant wiki pages.