Article (Scientific journals)
Atomic-Resolution Structure of a Class C β-Lactamase and Its Complex with Avibactam
Pozzi, C.; Di Pisa, F.; De Luca, F. et al.
2018In ChemMedChem, 13 (14), p. 1437-1446
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Keywords :
X-ray diffraction; Aeromonas; Aeromonas enteropelogenes; Article; Pseudomonas aeruginosa; Gram negative infection; X ray crystallography; Amino Acid Sequence; Azabicyclo Compounds; Crystallography, X-Ray; Drug Design; Gram-Negative Bacterial Infections; Humans; Molecular Docking Simulation; Protein Conformation; Sequence Alignment
Abstract :
[en] 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. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Disciplines :
Life sciences: Multidisciplinary, general & others
Biochemistry, biophysics & molecular biology
Microbiology
Author, co-author :
Pozzi, C.;  Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy
Di Pisa, F.;  Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy
De Luca, F.;  Department of Medical Biotechnology, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy
Benvenuti, M.;  Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy
Docquier, Jean-Denis ;  Université de Liège - ULiège > Département des sciences de la vie > Centre d'ingénierie des protéines
Mangani, S.;  Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy
Language :
English
Title :
Atomic-Resolution Structure of a Class C β-Lactamase and Its Complex with Avibactam
Publication date :
2018
Journal title :
ChemMedChem
ISSN :
1860-7179
eISSN :
1860-7187
Publisher :
John Wiley and Sons Ltd
Volume :
13
Issue :
14
Pages :
1437-1446
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 13 November 2020

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