Beta-lactamases and bacterial resistance to antibiotics.
The efficiency of beta-lactam antibiotics, which are among our most useful chemotherapeutic weapons, is continuously challenged by the emergence of resistant bacterial strains. This is most often due to the production of beta-lactamases by the resistant cells. These enzymes inactivate the antibiotics by hydrolysing the beta-lactam amide bond. The elucidation of the structures of some beta-lactamases by X-ray crystallography has provided precious insights into their catalytic mechanisms and revealed unsuspected similarities with the DD-transpeptidases, the bacterial enzymes which constitute the lethal targets of beta-lactams. Despite numerous kinetic, structural and site-directed mutagenesis studies, we have not completely succeeded in explaining the diversity of the specificity profiles of beta-lactamases and their surprising catalytic power. The solutions to these problems represent the cornerstones on which better antibiotics can be designed, hopefully on a rational basis.
Frère
J M
JM
Laboratoire d'Enzymologie and Centre d'Ingénierie des Protéines, Institut de Chimie, Université de Liège, Sart Tilman, Belgium.
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D010458:Peptidyl Transferases / Q000502:physiology; D011487:Protein Conformation; D012641:Selection, Genetic; D013329:Structure-Activity Relationship; D015032:Zinc / Q000502:physiology; D018440:beta-Lactam Resistance / Q000235:genetics; D001618:beta-Lactamases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D047090:beta-Lactams; D010458:Peptidyl Transferases; D001618:beta-Lactamases; D015032:Zinc