5FQC

Crystal structure of the metallo-beta-lactamase VIM-2 with 2C

Summary for 5FQC

• Entry DOI: 10.2210/pdb5fqc/pdb
• Related: 5FQ9
• Descriptor: BETA-LACTAMASE, FORMIC ACID, ZINC ION, ... (6 entities in total)
• Functional Keywords: hydrolase, antibiotic resistance
• Biological source: PSEUDOMONAS AERUGINOSA
• Total number of polymer chains: 2
• Total formula weight: 52755.96

Authors

Brem, J.,Cain, R.,McDonough, M.A.,Clifton, I.J.,Fishwick, C.W.G.,Schofield, C.J. (deposition date: 2015-12-08, release date: 2016-08-17, Last modification date: 2024-01-10)

Primary citation

Brem, J.,Cain, R.,Cahill, S.,McDonough, M.A.,Clifton, I.J.,Jimenez-Castellanos, J.C.,Avison, M.B.,Spencer, J.,Fishwick, C.W.,Schofield, C.J.
Structural basis of metallo-beta-lactamase, serine-beta-lactamase and penicillin-binding protein inhibition by cyclic boronates.
Nat Commun, 7:12406-12406, 2016

PubMed Abstract: β-Lactamases enable resistance to almost all β-lactam antibiotics. Pioneering work revealed that acyclic boronic acids can act as 'transition state analogue' inhibitors of nucleophilic serine enzymes, including serine-β-lactamases. Here we report biochemical and biophysical analyses revealing that cyclic boronates potently inhibit both nucleophilic serine and zinc-dependent β-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-β-lactamases, and which could also have antimicrobial activity through inhibition of PBPs.

PubMed: 27499424
DOI: 10.1038/ncomms12406

Experimental method

X-RAY DIFFRACTION (1.449 Å)