Inhibition of D-Ala:D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29208891.
- Also identified by DOI 10.1038/s41467-017-02118-7 and PMC identifier 5717164.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
D-cycloserine is an antibiotic which targets sequential bacterial cell wall peptidoglycan biosynthesis enzymes: alanine racemase and D-alanine:D-alanine ligase. By a combination of structural, chemical and mechanistic studies here we show that the inhibition of D-alanine:D-alanine ligase by the antibiotic D-cycloserine proceeds via a distinct phosphorylated form of the drug. This mechanistic insight reveals a bimodal mechanism of action for a single antibiotic on different enzyme targets and has significance for the design of future inhibitor molecules based on this chemical structure.
Medical subject headings
- Antibiotics, Antitubercular
- Cycloserine
- Peptide Synthases