β-Lactamases (BLs) are important antibiotic-resistance determinants that significantly compromise the efficacy of valuable β-lactam antibacterial drugs. Thus, combinations with BL inhibitor were developed. Avibactam is the first non-β-lactam BL inhibitor introduced into clinical practice. Ceftazidime–avibactam represents one of the few last-resort antibiotics available for the treatment of infections caused by near-pandrug-resistant bacteria. TRU-1 is a chromosomally encoded AmpC-type BL of Aeromonas enteropelogenes, related to the FOX-type BLs and constitutes a good model for class C BLs. TRU-1 crystals provided ultrahigh-resolution diffraction data for the native enzyme and for its complex with avibactam. A comparison of the native and avibactam-bound structures revealed new details in the conformations of residues relevant for substrate and/or inhibitor binding. Furthermore, a comparison of the TRU-1 and Pseudomonas aeruginosa AmpC avibactam-bound structures revealed two inhibitor conformations that were likely to correspond to two different states occurring during inhibitor carbamylation/recyclization.
|Titolo:||Atomic-Resolution Structure of a Class C β-Lactamase and Its Complex with Avibactam|
DOCQUIER, JEAN DENIS (Corresponding)
MANGANI, STEFANO (Corresponding)
|Citazione:||Pozzi, C., Di Pisa, F., De Luca, F., Benvenuti, M., Docquier, J.D., & Mangani, S. (2018). Atomic-Resolution Structure of a Class C β-Lactamase and Its Complex with Avibactam. CHEMMEDCHEM, 13(14), 1437-1446.|
|Appare nelle tipologie:||1.1 Articolo in rivista|