Off-the-shelf proteins that rival tailor-made antibodies as catalysts

MIMICKING the efficiency of enzyme catalysis is a daunting challenge. An enzyme selectively binds and stabilizes the transition state(s) for a particular reaction1,2. Artificial host systems can bind ground states just as efficiently3, 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 antibodies5,6. They bind transition-state analogues with high affinity, but their catalytic efficiency generally falls far short of that of enzymes4,8. Thorn et al.9 recently described an antibody that catalyses the eliminative ring-opening of a benzisoxazole "exceptionally efficiently" using car-boxylate as the general base, raising the intriguing possibility that this high efficiency derives from precise positioning of catalytic and substrate groups10. 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.