Enzymology takes a quantum leap forward.
Enzymes are biological molecules that accelerate chemical reactions. They are central to the existence of life. Since the discovery of enzymes just over a century ago, we have witnessed an explosion in our understanding of enzyme catalysis, leading to a more detailed appreciation of how they work. A key breakthrough came from understanding how enzymes surmount the potential-energy barrier that separates reactants from products. The genetic engineering revolution has provided tools for dissecting enzyme structure and enabling design of novel function. Despite the huge efforts to redesign enzyme molecules for specific applications, progress in this area has been generally disappointing. This stems from our limited understanding of the subtleties by which enzymes enhance reaction rates. Based on current dogma, the vast majority of studies have concentrated on understanding how enzymes facilitate passage of the reaction over a static potential-energy barrier. However, recent studies have revealed that passage through, rather than over, the barrier can occur. These studies reveal that quantum mechanical phenomena, driven by protein dynamics, can play a pivotal role in enzyme action. The new millennium will witness a flurry of activity directed at understanding the role of quantum mechanics and protein motion in enzyme action. We discuss these new developments and how they will guide enzymology into the new millennium.
Sutcliffe
Michael J
MJ
Department of Chemistry, University of Leicester, University Road, Leicester LE1 7RH, UK ( sjm@le.ac.uk ).
Scrutton
Nigel S
NS
Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10747-51
7938023
Biophys J. 1992 Sep;63(3):689-99
1420907
Q Rev Biophys. 1980 Nov;13(4):387-564
7015406
Nature. 1994 Aug 4;370(6488):389-91
8047147
Trends Biochem Sci. 1989 Mar;14(3):101-5
2658216
Biochemistry. 1976 Dec 14;15(25):5631-40
999839
Nature. 1990 Jan 4;343(6253):38-43
2296288
Biochemistry. 1999 Mar 9;38(10):3218-22
10074378
Biochemistry. 1997 Mar 4;36(9):2603-11
9054567
Biochemistry. 1989 Aug 8;28(16):6597-605
2790014
Science. 1988 Oct 28;242(4878):533-40
3051385
Nature. 1974 Sep 20;251(5472):200-4
4417076
Biophys J. 1966 Nov;6(6):825-47
5972381
Science. 1989 Mar 10;243(4896):1325-30
2646716
Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12360-5
9356454
Trends Biotechnol. 1998 Jun;16(6):258-64
9652137
Trends Biochem Sci. 1989 Apr;14(4):145-8
2658222
Biochemistry. 1994 Dec 13;33(49):14871-8
7993913
Biochim Biophys Acta. 1988 Jun 29;955(1):26-42
2838088
J Theor Biol. 1977 Nov 21;69(2):239-63
592874
Proc Natl Acad Sci U S A. 1978 Oct;75(10):4848-52
283394
Methods Enzymol. 1995;249:373-97
7791619
Science. 1990 Aug 3;249(4968):491-8
17735282
Sci Am. 1973 Oct;229(4):52-64
4727696
Adv Enzymol Relat Areas Mol Biol. 1978;46:415-94
345770
Biochem Mol Biol Int. 1994 Apr;32(5):831-9
8069232