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Nonspecific catalysis by protein surfaces
Authors:Anthony J. Kirby  Florian Hollfelder  Dan S. Tawfik
Affiliation:(1) University Chemical Laboratory, CB2 1EW Cambridge, UK;(2) Centre for Protein Engineering, Hills Road, CB2 2HQ Cambridge, UK
Abstract:Catalytic antibodies are the best availablea llaround enzyme mimics. They provide a unique experimental approach and some special insights into general questions about catalysis by enzymes. They offer enantiospecific reactions and levels of substrate binding that compare well with typical enzyme reactions, but not—so far—comparable catalytic efficiency. We and others have used the Kemp elimination as a probe of catalytic efficiency in antibodies. We compare these reactions with nonspecific catalysis by other proteins, and with catalysis by enzymes. Several simple reactions are catalyzed by theserum albumins with Michaelis-Menten kinetics, and can be shown to involve substrate binding and catalysis by local functional groups. Here, we report the details of one investigation, which implicate known binding sites on the protein surface and discuss implications for catalyst design and efficiency.
Keywords:Antibodies  catalysis  transition-state analog  albumin  BSA
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