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Welcome to the MurLigase wiki!

Many of the most effective antibiotics target fundamental pathways such as, bacterial cell wall biosynthesis, DNA replication and protein biosynthesis.

Mur ligase are a set of four Mur ubiquitin ligase enzymes: MurC, MurD, MurE, MurF which catalyze the addition of a short polypeptide to UDP-D-acetylmuramic acid in the process of bacterial cell wall buildup from peptidoglycans.
All four enzymes are topologically similar.

• MurC ligase or UDP-N-acetylmuramoyl-L-alanine ligase adds L-alanine to peptidoglycans.
• MurD ligase or UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase catalyzes the conversion of UDP-N-acetylmuramoyl-L-alanine (UMA), D-glutamate and ATP to UDP-N-acetylmuramoyl-L-alanine-D-glutamate and ADP. I.e. adds D-glutamate to peptidoglycans.
• MurE ligase or UDP-N-acetylmuramoyl-L-alaninyl-D-glutamate-2,6-diaminopimelate ligase adds meso-diaminpimelate to peptidoglycans.
• MurF ligase or UDP-N-acetylmuramoyl-L-alanine-D-glutamyl-lysine-D-alanyl-D-alanine ligase adds D-alanyl-D-alanine to peptidoglycans.

Target Validation

Current status of screening

MurC.

Not sure of status

MurD

X-chem screen, run by Dom Bellini. Re-screening? 4 hits on Fragalysis? Ian Gilbert says they are not tractable for elaboration, so is doing a new NMR screen. There have been 3-4 other frag screens, but not known?
Original ChrisD screen vs MurD was 250K compounds from MRC. No co-cryst. Medchem just made the compounds less soluble. PaulB has already found a decent way to go

MurE. Hits

On Fragalysis?

MurF

No hits reported. But has been done by LifeArc in the last year (NMR Leicester? Not Xchem?). Dom Bellini can make them available, or not?