Abstract:
: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.
journal_name
ChemMedChemjournal_title
ChemMedChemauthors
Pozzi C,Di Pisa F,De Luca F,Benvenuti M,Docquier JD,Mangani Sdoi
10.1002/cmdc.201800213subject
Has Abstractpub_date
2018-07-18 00:00:00pages
1437-1446issue
14eissn
1860-7179issn
1860-7187journal_volume
13pub_type
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