Structural basis for selective inhibition of antibacterial target MraY, a membrane-bound enzyme involved in peptidoglycan synthesis

Drug Discovery Today
Jenny HeringGisela Brändén

Abstract

The rapid growth of antibiotic-resistant bacterial infections is of major concern for human health. Therefore, it is of great importance to characterize novel targets for the development of antibacterial drugs. One promising protein target is MraY (UDP-N-acetylmuramyl-pentapeptide: undecaprenyl phosphate N-acetylmuramyl-pentapeptide-1-phosphate transferase or MurNAc-1-P-transferase), which is essential for bacterial cell wall synthesis. Here, we summarize recent breakthroughs in structural studies of bacterial MraYs and the closely related human GPT (UDP-N-acetylglucosamine: dolichyl phosphate N-acetylglucosamine-1-phosphate transferase or GlcNAc-1-P-transferase). We present a detailed comparison of interaction modes with the natural product inhibitors tunicamycin and muraymycin D2. Finally, we speculate on possible routes to design an antibacterial agent in the form of a potent and selective inhibitor against MraY.

Citations

Sep 1, 2019·The Journal of Antibiotics·Timothy D H Bugg, Rachel V Kerr
Jul 1, 2020·Antioxidants & Redox Signaling·Raffaella Bonavita, Mikko O Laukkanen
Jul 4, 2019·Nature Communications·Ellene H MashalidisSeok-Yong Lee
Aug 20, 2019·The Journal of Antibiotics·Neil P J PricePatrick F Dowd
Aug 16, 2019·Clinical Microbiology Reviews·Joaquim Ruiz
Dec 8, 2020·Frontiers in Cellular and Infection Microbiology·Moagi ShakuBavesh D Kana
Mar 23, 2020·Journal of Molecular Biology·Ellene H Mashalidis, Seok-Yong Lee
Dec 30, 2020·Chemical Reviews·Jed F Fisher, Shahriar Mobashery
Nov 10, 2020·ACS Chemical Biology·Jenny HeringMargareta Ek
Dec 1, 2021·Journal of Medicinal Chemistry·Wendy TranRichard J Payne

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Bacterial Cell Wall Structure (ASM)

Bacterial cell walls are made of peptidoglycan (also called murein), which is made from polysaccharide chains cross-linked by unusual peptides containing D-amino acids. Here is the latest research on bacterial cell wall structures.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Bacterial Protein Structures

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.

Bacterial Protein Structures (ASM)

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.

Bacterial Cell Wall Structure

Bacterial cell walls are made of peptidoglycan (also called murein), which is made from polysaccharide chains cross-linked by unusual peptides containing D-amino acids. Here is the latest research on bacterial cell wall structures.