Letter | Published:

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

Nature volume 383, pages 6063 (05 September 1996) | Download Citation

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Abstract

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.

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References

  1. 1.

    Chem. Eng. News 24, 1375–1377 (1946).

  2. 2.

    Enzyme Structure and Mechanism 2nd edn (Freeman, New York, 1985).

  3. 3.

    The Lock and Key Principle (ed. Behr, J.-P.) (Wiley, Chichester, 1994).

  4. 4.

    Angew. Chem. Int. Ed. Engl. 35, 707–724 (1996).

  5. 5.

    Annu. Rev. Biochem. 61, 29–54 (1992).

  6. 6.

    & Science 269, 1835–1842 (1995).

  7. 7.

    , & Molec. Biotechnol. 1, 87 (1994).

  8. 8.

    Acta Chem. Scand 50, 203–210 (1996).

  9. 9.

    , , & Nature 373, 228–230 (1995).

  10. 10.

    Nature 373, 196–197 (1995).

  11. 11.

    , , & J. Org. Chem. 38, 2294–2301 (1973).

  12. 12.

    Adv. Phys. Org. Chem. 17, 183–278 (1980).

  13. 13.

    & Science 267, 90–92 (1995).

  14. 14.

    & J. Chem. Soc., Perkin Trans. 2, 907–912 (1989).

  15. 15.

    & J. Chem. Soc., Perkin Trans. 2, 643–648 (1994).

  16. 16.

    & J. Chem. Soc., Perkin Trans. 2, 649–656 (1994).

  17. 17.

    & J. Chem. Soc. Chem. Commun. 707–708 (1994).

  18. 18.

    , & J. Am. Chem. Soc. 97, 7312–7318 (1975).

  19. 19.

    & Adv. Prot. Chem. 45, 153–203 (1994).

  20. 20.

    & Nature 358, 209–215 (1992).

  21. 21.

    , & Molec. Pharmacol. 11, 824–832 (1975).

  22. 22.

    , , & J. Am. Chem. Soc. 97, 1934–1943 (1975).

  23. 23.

    & J. Biol. Chem. 237, 1113–1120 (1962).

  24. 24.

    et al. Isr. J. Chem. (in the press).

  25. 25.

    & J. Am. Chem. Soc. 109, 3145–3146 (1987).

  26. 26.

    & Biochemistry 14, 4989–4994 (1975).

  27. 27.

    & J. Am. Chem. Soc. 95, 5819–5820 (1973).

  28. 28.

    , , & J. Am. Chem. Soc. 97, 1943–1948 (1975).

  29. 29.

    Enzyme Assays (eds Eisenthal, R. & Danson, M. J.) (Oxford University Press, New York, 1993).

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Author information

Affiliations

  1. University Chemical Laboratory, Cambridge CB2 1EW, UK

    • Florian Hollfelder
    • , Anthony J. Kirby
    •  & Dan S. Tawfik

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https://doi.org/10.1038/383060a0

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