IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
artículos
Título:
Shaping substrate selectivity in a broad spectrum metallo-β-lactamase
Autor/es:
L. J. GONZÁLEZ ; D.M. MORENO ; C. STIVAL ; VILA AJ; C. STIVAL ; VILA AJ; J.L. PUZZOLO; J.L. PUZZOLO; L. J. GONZÁLEZ ; D.M. MORENO
Revista:
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Editorial:
AMER SOC MICROBIOLOGY
Referencias:
Año: 2018 vol. 62
ISSN:
0066-4804
Resumen:
Metallo--lactamases (MBLs) are the major group of carbapenemasesproduced by bacterial pathogens. The design of MBL inhibitors has been limitedby, among other issues, incomplete knowledge about how these enzymes modulatesubstrate recognition. While most MBLs are broad-spectrum enzymes, B2 MBLsare exclusive carbapenemases. This narrower substrate profile has been attributed toa sequence insertion present in B2 enzymes that limits accessibility to the activesite. In this work, we evaluate the role of sequence insertions naturally occurring inthe B2 enzyme Sfh-I and in the broad-spectrum B1 enzyme SPM-1. We engineered achimeric protein in which the sequence insertion of SPM-1 was replaced by the onepresent in Sfh-I. The chimeric variant is a selective cephalosporinase, revealing thatthe substrate profile of MBLs can be further tuned depending on the protein context.These results also show that the stable scaffold of MBLs allows a modular engineeringmuch richer than the one observed in nature.