In Vivo Evolution of a β-lactamase-like Activity Throughout the Idiotypic Pathway

Abstract

An abzyme (9G4H9) displaying a β-lactamase activity was obtained through the idiotypic pathway and has been previously described. Analysis of the catalytic mechanism by kinetic measurements with various substrates, chemical modifications, and three dimensional modeling, led us to conclude that IgG 9G4H9 displays an activity at the crossroads of β-lactamases and penicillin-binding proteins (PBPs). Penicillin-binding proteins and βlactamases are two closely related enzymes arising from a common ancestral gene. We herein propose that the idiotypic network has allowed the generation of a catalyst with unique catalytic properties, but that could behave as an intermediate between both enzymes.

Keywords::

• Abzyme
• Catalytic antibody
• Anti-idiotypic antibody
• β-lactamase
• Penicillin-binding protein
• Molecular evolution