Nature 350, 121 - 124 (14 March 1991); doi:10.1038/350121a0

Enzyme catalysis: not different, just better

Jeremy R. Knowles

Departments of Chemistry and Biochemistry, Harvard University, Cambridge, Massachusetts 02138, USA.

Where are we in our understanding of enzyme catalysis? The gloomier view is that protein structure and enzyme function are the finely balanced end-products of many weak interactions that can be summed only by massive computing power, and more precise parameterization than we enjoy at present. The cheerier position is that proteins are built on definable principles, and that enzymes use recognizable catalytic devices that will allow us to understand how existing enzymes work and to design new ones. To assess which interpretation is the more realistic, the simple reaction catalysed by triosephosphate isomerase is considered here. This examination illustrates some of the catalytic features of enzymes that are understood, and exposes a few that are not. But overall, the question turns out to have an optimistic answer.

References

1.	Rieder, S. V. & Rose, I. A. J. biol. Chem. 234, 1007−1010 (1959). | PubMed | ChemPort |
2.	Rose, I. A. Brookhaven Symp. Biol. 15, 293−309 (1962). | PubMed | ChemPort |
3.	Maister, S. G., Pett, C. P., Albery, W. J. & Knowles, J. R. Biochemistry 15, 5607−5612 (1976). | Article | PubMed | ChemPort |
4.	Richard, J. P. J. Am. chem. Soc. 106, 4926−4936 (1984). | Article | ChemPort |
5.	Adams, M. J. et al. Proc. natn. Acad. Sci. U.S.A 70, 1968−1972 (1973). | ChemPort |
6.	Clarke, A. R. et al. Nature 324, 699−702 (1986). | Article | PubMed | ISI | ChemPort |
7.	Ludwig, M. L. et al. Proc. natn. Acad. Sci. U.S.A. 57, 511−514 (1967). | ChemPort |
8.	Bennett, W. S. Jr & Steitz, T. A. Proc. natn. Acad. Sci. U.S.A. 75, 4848−4852 (1978). | ChemPort |
9.	Pickover, C. A., McKay, D. B., Engelman, D. M. & Steitz, T. A. J. biol. Chem. 254, 11323−11329 (1979). | PubMed | ChemPort |
10.	Winn, S. I., Watson, H. C., Harkins, R. N. & Fothergill, L. A. Phil. Trans. R. Soc. B293, 121−130 (1981).
11.	Banner, D. W. et al. Nature 255, 609−614 (1976).
12.	Alber, T. C. et al. Phil. Trans. R. Soc. B293, 159−171 (1981).
13.	Lolis, E. & Petsko, G. A. Biochemistry 29, 6619−6625 (1990). | Article | PubMed | ISI | ChemPort |
14.	Joseph, D., Petsko, G. A. & Karplus, M. Science 249, 1425−1428 (1990). | PubMed | ISI | ChemPort |
15.	Pompliano, D. L., Peyman, A. & Knowles, J. R. Biochemistry 29, 3186−3194 (1990). | Article | PubMed | ChemPort |
16.	Möller, W. & Amons, R. FEBS Lett. 186, 1−7 (1985). | Article | PubMed | ISI | ChemPort |
17.	Wierenga, R. K., Terpstra, P. & Hol, G. J. J. molec. Biol. 187, 101−107 (1986). | Article | PubMed | ChemPort |
18.	Seeburg, P. H., Colby, W. W., Capon, D. H., Goeddel, D. V. & Levinson, A. D. Nature 312, 71−75 (1984). | Article | PubMed | ISI | ChemPort |
19.	Reinstein, J., Brune, M. & Wittinghofer, A. Biochemistry 27, 4712−4720 (1988). | Article | PubMed | ISI | ChemPort |
20.	Redfield, A. G. & Papastavros, M. Z. Biochemistry 29, 3509−3514 (1990). | Article | PubMed | ChemPort |
21.	Saraste, M., Sibbald, P. R. & Wittinghofer, A. Trends biol. Sci. 15, 430−434 (1990). | Article |
22.	Davenport, R. C. thesis, MIT, Cambridge, Massachusetts (1986).
23.	Alber, T. C. et al. Cold Spring Harbor Symp. quant. Biol. 52, 603−613 (1987). | PubMed | ChemPort |
24.	Corey, E. J. & Sneen, R. A. J. Am. chem. Soc. 78, 6269−6278 (1956). | Article | ChemPort |
25.	Gandour, R. D. Bioorg. Chem. 10, 169−176 (1987).
26.	Raines, R. T., Sutton, E. L., Straus, D. R., Gilbert, W. & Knowles, J. R. Biochemistry 25, 7142−7154 (1986). | Article | PubMed | ChemPort |
27.	Zimmerman, S. C. & Cramer, K. D. J. Am. chem. Soc. 110, 5906−5908 (1988). | Article | ChemPort |
28.	Huff, J. B., Askew, B., Duff, R. J. & Rebek, J. J. Am. chem. Soc. 110, 5908−5909 (1988). | Article | ChemPort |
29.	Webb, M. R. & Knowles, J. R. Biochem. J. 141, 589−592 (1974). | PubMed | ChemPort |
30.	Belasco, J. G. & Knowles, J. R. Biochemistry 19, 472−477 (1980). | Article | PubMed | ChemPort |
31.	Nickbarg, E. B., Davenport, R. C., Petsko, G. A. & Knowles, J. R. Biochemistry 27, 5948−5960 (1988). | Article | PubMed | ISI | ChemPort |
32.	Blacklow, S. C. & Knowles, J. R. Biochemistry 29, 4099−4108 (1990). | Article | PubMed | ChemPort |
33.	Komives, E. A. et al. Biochemistry (in the press).
34.	Bachovchin, W. W. Biochemistry 25, 7751−7759 (1986). | Article | PubMed | ISI | ChemPort |
35.	Hol, W. G. J. Prog. biophys. molec. Biol. 45, 149−195 (1985). | Article | ISI | ChemPort |
36.	Tidor, B. & Karplus, M. Biochemistry (in the press).
37.	Perutz, M. F., Gronenborn, A. M., Clore, G. M., Fogg, J. H. & Shih, D. T.-b. J. molec. Biol. 183, 491−498 (1985). | Article | PubMed | ISI | ChemPort |
38.	Sali, D., Bycroft, M. & Fersht, A. R. Nature 335, 740−743 (1988). | Article | PubMed | ChemPort |
39.	Belasco, J. G., Herlihy, J. M. & Knowles, J. R. Biochemistry 17, 2971−2978 (1978). | Article | PubMed | ChemPort |
40.	Blow, D. M. & Smith, J. M. Phil. Trans. R. Soc. B272, 87−97 (1975).
41.	Haldane, J. B. S. in Enzymes 182 (Longmans, London, 1930).
42.	Pauling, L. Chem. Eng. News 24, 1375−1377 (1946). | ChemPort |
43.	Leatherbarrow, R. J., Fersht, A. R. & Winter, G. Proc. natn. Acad. Sci. U.S.A. 82, 7840−7844 (1985). | ChemPort |
44.	Fischer, E. Ber. dtsch chem. Ges. 27, 2985−2993 (1894).
45.	Albery, W. J. & Knowles, J. R. Biochemistry 15, 5627−5631 (1976). | Article | PubMed | ChemPort |