Structural highlights
Function
MRAY_ECOLI Catalyzes the initial step of the lipid cycle reactions in the biosynthesis of the cell wall peptidoglycan: transfers peptidoglycan precursor phospho-MurNAc-pentapeptide from UDP-MurNAc-pentapeptide onto the lipid carrier undecaprenyl phosphate, yielding undecaprenyl-pyrophosphoryl-MurNAc-pentapeptide, known as lipid I.[HAMAP-Rule:MF_00038][1] [2]
Publication Abstract from PubMed
The historically important phage PhiX174 kills its host bacteria by encoding a 91-residue protein antibiotic called protein E. Using single-particle electron cryo-microscopy, we demonstrate that protein E bridges two bacterial proteins to form the transmembrane YES complex [MraY, protein E, sensitivity to lysis D (SlyD)]. Protein E inhibits peptidoglycan biosynthesis by obstructing the MraY active site leading to loss of lipid I production. We experimentally validate this result for two different viral species, providing a clear model for bacterial lysis and unifying previous experimental data. Additionally, we characterize the Escherichia coli MraY structure-revealing features of this essential enzyme-and the structure of the chaperone SlyD bound to a protein. Our structures provide insights into the mechanism of phage-mediated lysis and for structure-based design of phage therapeutics.
The mechanism of the phage-encoded protein antibiotic from PhiX174.,Orta AK, Riera N, Li YE, Tanaka S, Yun HG, Klaic L, Clemons WM Jr Science. 2023 Jul 14;381(6654):eadg9091. doi: 10.1126/science.adg9091. Epub 2023 , Jul 14. PMID:37440661[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ikeda M, Wachi M, Jung HK, Ishino F, Matsuhashi M. The Escherichia coli mraY gene encoding UDP-N-acetylmuramoyl-pentapeptide: undecaprenyl-phosphate phospho-N-acetylmuramoyl-pentapeptide transferase. J Bacteriol. 1991 Feb;173(3):1021-6. PMID:1846850 doi:10.1128/jb.173.3.1021-1026.1991
- ↑ Geis A, Plapp R. Phospho-N-acetylmuramoyl-pentapeptide-transferase of Escherichia coli K12. Properties of the membrane-bound and the extracted and partially purified enzyme. Biochim Biophys Acta. 1978 Dec 8;527(2):414-24. PMID:215212 doi:10.1016/0005-2744(78)90355-8
- ↑ Orta AK, Riera N, Li YE, Tanaka S, Yun HG, Klaic L, Clemons WM Jr. The mechanism of the phage-encoded protein antibiotic from ΦX174. Science. 2023 Jul 14;381(6654):eadg9091. PMID:37440661 doi:10.1126/science.adg9091
