Internet Archive Scholar

Critical Impact of Peptidoglycan Precursor Amidation on the Activity of l,d -Transpeptidases from Enterococcus faecium and Mycobacterium tuberculosis

Flora Ngadjeua, Emmanuelle Braud, Saidbakhrom Saidjalolov, Laura Iannazzo, Dirk Schnappinger, Sabine Ehrt, Jean-Emmanuel Hugonnet, Dominique Mengin-Lecreulx, Delphine Patin, Mélanie Ethève-Quelquejeu, Matthieu Fonvielle, Michel Arthur
2018 Chemistry - A European Journal  

Preserved Fulltext

fulltext thumbnail
Web Archive Capture PDF (2.4 MB)
https://web.archive.org/web/20190428040655/https://hal.sorbonne-universite.fr/hal-01817697/file/ARTHUR_Michel.pdf

A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2019; you can also visit the original URL. The file type is application/pdf.

The bacterial cell wall peptidoglycan contains unusual L and D amino acids assembled in branched peptides. Insight into the biosynthesis of the polymer has been hampered by limited access to substrates and to suitable polymerization assays. Here we report the full synthesis of the peptide stem of peptidoglycan precursors from two pathogenic bacteria, Enterococcus faecium and Mycobacterium tuberculosis, and the development of a sensitive post-derivatization assay for their cross-linking by
more » ... anspeptidases. Access to series of stem peptides showed that amidation of free carboxyl groups is essential for optimal enzyme activity, in particular the amidation of diaminopimelate (DAP) residues for the cross-linking activity of the L,D-transpeptidase LdtMt2 from M. tuberculosis. Accordingly, construction of a conditional mutant established the essentiality of AsnB indicating that this DAP amidotransferase is an attractive target for the development of anti-mycobacterial drugs.
doi:10.1002/chem.201706082 pmid:29389045 fatcat:nqpv3prpyfdorht3plnj7tggp4
Citation

Flora Ngadjeua, Emmanuelle Braud, Saidbakhrom Saidjalolov, Laura Iannazzo, Dirk Schnappinger, Sabine Ehrt, Jean-Emmanuel Hugonnet, Dominique Mengin-Lecreulx, Delphine Patin, Mélanie Ethève-Quelquejeu, Matthieu Fonvielle, Michel Arthur. "Critical Impact of Peptidoglycan Precursor Amidation on the Activity of l,d -Transpeptidases from Enterococcus faecium and Mycobacterium tuberculosis." Chemistry - A European Journal 24.22 (2018) 5743-5747