Phospho-MurNAc-Pentapeptide Translocase (MraY) as a Target for Antibacterial Agents and Antibacterial Proteins

Title: Phospho-MurNAc-Pentapeptide Translocase (MraY) as a Target for Antibacterial Agents and Antibacterial Proteins

Volume: 6 Issue: 2

Author(s): Timothy D.H. Bugg, Adrian J. Lloyd and David I. Roper

Affiliation:

Keywords: Peptidoglycan biosynthesis, antibacterial agents, MraY, high-throughput screening

Abstract: Phospho-MurNAc-pentapeptide translocase (MraY, translocase I) catalyses the first step of the lipid-linked cycle of reactions of bacterial peptidoglycan biosynthesis. MraY is the target for five families of nucleoside antibacterial natural products: the tunicamycins, the mureidomycins (also pacidamycins, napsamycins), the liposidomycins, the muraymycins, and the capuramycins. Recent structure-activity studies on these families have led to the identification of active pharmacophores, and insight into their mechanisms of action. This step of peptidoglycan biosynthesis is also the target for the bacteriolytic E protein from bacteriophage φX174, and for cyclic peptides of the amphomycin family which complex the undecaprenyl phosphate co-substrate. The mechanisms of enzyme inhibition by these agents are discussed, and the state of knowledge regarding the transmembrane structure, active site, and catalytic mechanism of MraY. The availability of high throughput assays and prospects of MraY as an antibacterial target are also discussed.

Cite this article as:

Bugg D.H. Timothy, Lloyd J. Adrian and Roper I. David, Phospho-MurNAc-Pentapeptide Translocase (MraY) as a Target for Antibacterial Agents and Antibacterial Proteins, Infectious Disorders - Drug Targets 2006; 6 (2) . https://dx.doi.org/10.2174/187152606784112128