Structural highlights
Function
DACA_ECOLI Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors.
Publication Abstract from PubMed
beta-Lactamases enable resistance to almost all beta-lactam antibiotics. Pioneering work revealed that acyclic boronic acids can act as 'transition state analogue' inhibitors of nucleophilic serine enzymes, including serine-beta-lactamases. Here we report biochemical and biophysical analyses revealing that cyclic boronates potently inhibit both nucleophilic serine and zinc-dependent beta-lactamases by a mechanism involving mimicking of the common tetrahedral intermediate. Cyclic boronates also potently inhibit the non-essential penicillin-binding protein PBP 5 by the same mechanism of action. The results open the way for development of dual action inhibitors effective against both serine- and metallo-beta-lactamases, and which could also have antimicrobial activity through inhibition of PBPs.
Structural basis of metallo-beta-lactamase, serine-beta-lactamase and penicillin-binding protein inhibition by cyclic boronates.,Brem J, Cain R, Cahill S, McDonough MA, Clifton IJ, Jimenez-Castellanos JC, Avison MB, Spencer J, Fishwick CW, Schofield CJ Nat Commun. 2016 Aug 8;7:12406. doi: 10.1038/ncomms12406. PMID:27499424[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Brem J, Cain R, Cahill S, McDonough MA, Clifton IJ, Jimenez-Castellanos JC, Avison MB, Spencer J, Fishwick CW, Schofield CJ. Structural basis of metallo-beta-lactamase, serine-beta-lactamase and penicillin-binding protein inhibition by cyclic boronates. Nat Commun. 2016 Aug 8;7:12406. doi: 10.1038/ncomms12406. PMID:27499424 doi:http://dx.doi.org/10.1038/ncomms12406
