E. coli ribosome tweak targets antibiotics
- Vanderbilt researchers Andrew Rice and Yanqing Xue reported they identified YcaO as the enzyme that installs a rare sulfur swap on E. coli ribosomal protein uL16. - The March 12 Biochemistry paper says YcaO singled out uL16 from roughly 4,400 E. coli proteins and linked the tweak to ribosome growth behavior. - The modification sits near the ribosome’s catalytic core and also appears in pathogens including Klebsiella and Pseudomonas. (pubmed.ncbi.nlm.nih.gov)
Bacteria build proteins with ribosomes, molecular factories that read RNA and stitch amino acids into chains. A new Biochemistry paper identifies the enzyme behind a rare ribosome modification in Escherichia coli. (pubmed.ncbi.nlm.nih.gov) The modification is called thioamidation: one oxygen atom in a protein backbone bond is replaced with sulfur. In this case, it appears on ribosomal protein uL16, part of the large ribosomal subunit. (medschool.vanderbilt.edu) (pubmed.ncbi.nlm.nih.gov) That swap sits near the peptidyl transferase center, the ribosome’s catalytic heart where peptide bonds are formed. Because many antibiotics work by jamming bacterial ribosomes, changes near that site draw immediate interest. (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov) Andrew Rice, Yanqing Xue and colleagues at Vanderbilt used AlphaFold3 to model YcaO against the full E. coli proteome. Out of about 4,400 proteins, uL16 was the only one predicted to make a high-confidence, catalytically competent complex with YcaO. (medschool.vanderbilt.edu) (pubmed.ncbi.nlm.nih.gov) The team then tested that prediction with mutational analysis of the YcaO-uL16 interface. Their paper assigns E. coli YcaO as the enzyme responsible for the uL16 thioamide. (pubmed.ncbi.nlm.nih.gov) The paper also reports a “complex, nonlinear” relationship between this thioamide and a neighboring uL16 change, β-hydroxylation at Arg81, during log-phase growth. That finding ties the tweak to the way the ribosome is regulated, not just its static structure. (pubmed.ncbi.nlm.nih.gov) This is not a new antibiotic and not a new drug target validated in patients. It is a map of a bacterial-only feature that sits close to the machinery many existing antibiotics already attack. (medschool.vanderbilt.edu) (pmc.ncbi.nlm.nih.gov) That bacterial selectivity is central to the appeal. The Vanderbilt team said they believe neither YcaO nor this thioamidation is present in eukaryotes, the group of organisms that includes humans. (medschool.vanderbilt.edu) The researchers also extended the finding beyond laboratory E. coli. Bioinformatics predicted the same uL16 thioamidation in several thousand Pseudomonadota species, and the team validated it in Klebsiella pneumoniae and Pseudomonas aeruginosa. (pubmed.ncbi.nlm.nih.gov) The underlying ribosome structure has been studied for years at high resolution, but the enzyme behind this sulfur-for-oxygen swap had remained unknown. The new paper closes that gap and gives antibiotic researchers a more precise piece of the bacterial translation machinery to watch. (nature.com) (pubmed.ncbi.nlm.nih.gov)
