title: Off-the-shelf proteins that rival tailor-made antibodies as catalysts.
abstract: Mimicking the efficiency of enzyme catalysis is a daunting challenge. An enzyme selectively binds and stabilizes the transition state (s) for a particular reaction. Artificial host systems can bind ground states just as efficiently, and rate enhancements comparable to those in enzymatic reactions can be achieved by bringing catalytic and substrate groups together in intramolecular reactions. But the combination of selective binding and efficient catalysis remains elusive. The best enzyme mimics currently known are catalytic antibodies. They bind transition-state analogues with high affinity, but their catalytic efficiency generally falls far short of that of enzymes. Thorn et al. recently described an antibody that catalyses the eliminative ring-opening of a benziosoxazole "exceptionally efficiently" using carboxylate as the general base, raising the intriguing possibility that this high efficiency derives from precise positioning of catalytic and substrate groups. Here we show that familiar 'off-the-shelf' proteins--serum albumins--catalyse the same reaction at similar rates, using a lysine side-chain amino group as the catalytic general base. Comparisons suggest that formal general base catalysis is of only modest efficiency in both systems, and that the antibody catalysis is boosted by a non-specific medium effect.
authors.affiliation: University Chemical Laboratory, Cambridge, United Kingdom.
authors.forename: F
authors.initials: F
authors.lastname: Hollfelder
authors.forename: A J
authors.initials: AJ
authors.lastname: Kirby
authors.forename: D S
authors.initials: DS
authors.lastname: Tawfik
mesh_terms: D000818:Animals; D017151:Antibodies, Catalytic / Q000378:metabolism*; D002384:Catalysis; D002417:Cattle; D004798:Enzymes / Q000378:metabolism; D006736:Horses; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000378:metabolism; D018716:Molecular Mimicry; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: D017151:Antibodies, Catalytic; D004798:Enzymes; D012709:Serum Albumin; D008239:Lysine