6FM6

Crystal structure of the class C beta-lactamase TRU-1 from Aeromonas enteropelogenes

Summary for 6FM6

• Entry DOI: 10.2210/pdb6fm6/pdb
• Descriptor: Beta-lactamase, SULFATE ION, TRIETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: class c, serine beta-lactamase, tru-1, aeromonas enteropelogenes, hydrolase
• Biological source: Aeromonas enteropelogenes (Aeromonas trota)
• Total number of polymer chains: 1
• Total formula weight: 42260.15

Authors

Pozzi, C.,De Luca, F.,Di Pisa, F.,Benvenuti, M.,Docquier, J.D.,Mangani, S. (deposition date: 2018-01-30, release date: 2018-05-30, Last modification date: 2024-01-17)

Primary citation

Pozzi, C.,Di Pisa, F.,De Luca, F.,Benvenuti, M.,Docquier, J.D.,Mangani, S.
Atomic-Resolution Structure of a Class C beta-Lactamase and Its Complex with Avibactam.
ChemMedChem, 13:1437-1446, 2018

PubMed 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.

PubMed: 29786960
DOI: 10.1002/cmdc.201800213

Experimental method

X-RAY DIFFRACTION (1.05 Å)