A Structure-Based Classification of Class A β-Lactamases, a Broadly Diverse Family of Enzymes.
For medical biologists, sequencing has become a commonplace technique to support diagnosis. Rapid changes in this field have led to the generation of large amounts of data, which are not always correctly listed in databases. This is particularly true for data concerning class A β-lactamases, a group of key antibiotic resistance enzymes produced by bacteria. Many genomes have been reported to contain putative β-lactamase genes, which can be compared with representative types. We analyzed several hundred amino acid sequences of class A β-lactamase enzymes for phylogenic relationships, the presence of specific residues, and cluster patterns. A clear distinction was first made between dd-peptidases and class A enzymes based on a small number of residues (S70, K73, P107, 130SDN132, G144, E166, 234K/R, 235T/S, and 236G [Ambler numbering]). Other residues clearly separated two main branches, which we named subclasses A1 and A2. Various clusters were identified on the major branch (subclass A1) on the basis of signature residues associated with catalytic properties (e.g., limited-spectrum β-lactamases, extended-spectrum β-lactamases, and carbapenemases). For subclass A2 enzymes (e.g., CfxA, CIA-1, CME-1, PER-1, and VEB-1), 43 conserved residues were characterized, and several significant insertions were detected. This diversity in the amino acid sequences of β-lactamases must be taken into account to ensure that new enzymes are accurately identified. However, with the exception of PER types, this diversity is poorly represented in existing X-ray crystallographic data.
Faculté de Médecine Paris Descartes, Service de Bactériologie, Paris, France philippona@free.fr.
Alain
A
Philippon
Independent Researcher, Paris, France.
Patrick
P
Slama
Université Paris 3, UFR SMBH, Groupe des Hôpitaux Universitaires Paris-Seine Saint Denis, Centre de Recherches en Cancérologie de Lyon INSERM U1052 UMR CNRS 5286, Lyon, France.
Paul
P
Dény
Laboratoire Universitaire de Biodiversité et d'Ecologie Microbienne, Quimper, France.
Roger
R
Labia
D001419:Bacteria / Q000201:enzymology*; D018360:Crystallography, X-Ray; D014644:Genetic Variation; D005838:Genotype; D010802:Phylogeny; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D001618:beta-Lactamases / Q000737:chemistry / Q000145:classification* / Q000235:genetics* / Q000378:metabolism
D001618:beta-Lactamases