Structure-Function Relationships of Class D Carbapenemases

Acinetobacter baumannii; Antibiotic resistance; Beta-lactamases; Carbapenems; Klebsiella pneumoniae; Article; Burkholderia multivorans; Enterobacter cloacae; Francisella philomiragia; Francisella tularensis; Pseudomonas fluorescens; Serratia marcescens; X ray crystallography; Bacterial Proteins; Catalytic Domain; Crystallography, X-Ray; Humans; Models, Molecular; Mutation; Phylogeny; Protein Conformation

Abstract :

[en] Class D carbapenemases, also known as Carbapenem-Hydrolyzing class D β-Lactamases (CHDLs) are of increasingly high clinical relevance, as they have been found in various important human pathogens, such as Acinetobacter baumannii and Klebsiella pneumoniae and contribute to the evolution of these pathogens towards extensively or totally-drug resistance (XDR/TDR) phenotypes. Essentially two main groups of phylogenetically-related enzymes have been described: one including the acquired OXA-23, OXA-24/40, OXA-51 and OXA-58 enzymes mostly in Acinetobacter baumannii, and the other including the OXA-48-related variants, i.e. OXA-54, OXA-162, OXA-163 and OXA- 181. In this article, the biochemical and structural features of class D carbapenemases will be discussed. Furthermore, the mechanistic hypothesis based on recently obtained crystal structures of the native forms of class D carbapenemases and mutants thereof, in complex with relevant substrates or inhibitors, will be critically reviewed. Finally, the mechanism of inhibition by available inhibitors, some of which are currently in clinical development, will be discussed. © 2016 Bentham Science Publishers.

Disciplines :

Life sciences: Multidisciplinary, general & others
Biochemistry, biophysics & molecular biology
Microbiology

Author, co-author :

Docquier, Jean-Denis ; Université de Liège - ULiège > Département des sciences de la vie > Centre d'ingénierie des protéines

Mangani, S.; Dipartimento di Biotecnologie, Chimica e Farmacia, University of Siena, Siena, Italy

Language :

English

Title :

Structure-Function Relationships of Class D Carbapenemases

Publication date :

2016

Journal title :

Current Drug Targets

ISSN :

1389-4501

eISSN :

1873-5592

Publisher :

Bentham Science Publishers B.V.

Volume :

Issue :

Pages :

1061-1071

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 19 November 2020

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