Sutcliffe Michael J, Scrutton Nigel S
Department of Chemistry, University of Leicester, University Road, Leicester LE1 7RH, UK (
Philos Trans A Math Phys Eng Sci. 2000 Jan 15;358(1766):367-386. doi: 10.1098/rsta.2000.0536.
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.
酶是加速化学反应的生物分子。它们是生命存在的核心。自一个多世纪前发现酶以来,我们对酶催化作用的理解有了突飞猛进的发展,从而对它们的工作方式有了更详细的认识。一个关键的突破来自于了解酶是如何跨越将反应物与产物分开的势能屏障的。基因工程革命提供了剖析酶结构和设计新功能的工具。尽管为将酶分子重新设计用于特定应用付出了巨大努力,但该领域的进展总体上令人失望。这源于我们对酶提高反应速率的微妙之处了解有限。基于当前的教条,绝大多数研究都集中在理解酶如何促进反应越过静态势能屏障。然而,最近的研究表明,可以发生穿过而不是越过屏障的情况。这些研究表明,由蛋白质动力学驱动的量子力学现象在酶的作用中可以发挥关键作用。新千年将见证一系列旨在理解量子力学和蛋白质运动在酶作用中的作用的活动。我们讨论这些新进展以及它们将如何引导酶学进入新千年。