Kinetic Studies on CphA Mutants Reveal the Role of the P158-P172 Loop in Activity versus Carbapenems

Site-directed mutagenesis of CphA indicated that prolines in the P158-P172 loop are essential for the stability and the catalytic activity of subclass B2 metallo-β-lactamases against carbapenems. The sequential substitution of proline led to a decrease of the catalytic efficiency of the variant comp...

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Veröffentlicht in:	Antimicrobial agents and chemotherapy 2016-05, Vol.60 (5), p.3123-3126
Hauptverfasser:	Bottoni, Carlo, Perilli, Mariagrazia, Marcoccia, Francesca, Piccirilli, Alessandra, Pellegrini, Cristina, Colapietro, Martina, Sabatini, Alessia, Celenza, Giuseppe, Kerff, Frédéric, Amicosante, Gianfranco, Galleni, Moreno, Mercuri, Paola Sandra
Format:	Artikel
Sprache:	eng
Schlagworte:	Amino Acid Sequence Bacterial Proteins Bacterial Proteins - genetics Bacterial Proteins - metabolism beta-Lactamases beta-Lactamases - chemistry beta-Lactamases - genetics beta-Lactamases - metabolism Binding Sites Biochemistry, biophysics & molecular biology Biochimie, biophysique & biologie moléculaire Carbapenems Carbapenems - pharmacology Kinetics Life sciences Mechanisms of Resistance Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Proline - chemistry Proline - metabolism Sciences du vivant Sequence Analysis, Protein Structure-Activity Relationship Substrate Specificity - genetics Substrate Specificity - physiology Zinc - pharmacology
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Zusammenfassung:	Site-directed mutagenesis of CphA indicated that prolines in the P158-P172 loop are essential for the stability and the catalytic activity of subclass B2 metallo-β-lactamases against carbapenems. The sequential substitution of proline led to a decrease of the catalytic efficiency of the variant compared to the wild-type (WT) enzyme but also to a higher affinity for the binding of the second zinc ion.
ISSN:	0066-4804 1098-6596 1098-6596
DOI:	10.1128/AAC.01703-15