Post by Amr El-Araby

Excited to share a new publication from my doctoral research, now published in 𝑨𝑪𝑺 𝑪𝒂𝒕𝒂𝒍𝒚𝒔𝒊𝒔! 📚 Title: "Catalytic Cycle of 𝘕-Acetylmuramic Acid-α-1-Phosphate Uridylyltransferase MurU of 𝘗𝘴𝘦𝘶𝘥𝘰𝘮𝘰𝘯𝘢𝘴 𝘢𝘦𝘳𝘶𝘨𝘪𝘯𝘰𝘴𝘢" 🔗 Link: https://lnkd.in/gRwzjqfR Gram-negative bacteria continuously remodel their cell wall as they grow and divide. Rather than discard the resulting fragments, these organisms recover and recycle them through a dedicated cytoplasmic pathway. This recycling process contributes to antimicrobial resistance, making it an attractive target for new therapeutic strategies. In this study, we investigated MurU, the uridylyltransferase responsible for the final step of cell-wall recycling in the highly resistant pathogen 𝘗𝘴𝘦𝘶𝘥𝘰𝘮𝘰𝘯𝘢𝘴 𝘢𝘦𝘳𝘶𝘨𝘪𝘯𝘰𝘴𝘢. Through structural, kinetic, and mechanistic studies, we found that MurU sits at the intersection of cell-wall recycling and 𝘥𝘦 𝘯𝘰𝘷𝘰 cell-wall biosynthesis. Its relatively slow catalytic activity compared with other characterized enzymes in the pathway ssuggest that MurU may be an important control point in the recycling pathway. This highlights MurU as a promising target for antibiotic-adjuvant development. This work is another product of the long-standing collaboration between the Mobashery laboratory at the University of Notre Dame - College of Science and the Hermoso laboratory at Instituto de Química Física Blas Cabrera (IQF-CSIC). I am grateful to all collaborators who contributed to this project. A special thank you to my co-first author, Eva Jiménez Faraco, whose outstanding work was instrumental to its success. #AntimicrobialResistance #ChemicalBiology #Microbiology #DrugDiscovery #StructuralBiology #Enzymology