Evolution of Enzyme Function and the Development of Catalytic Efficiency: Triosephosphate Isomerase, Jeremy R. Knowles, and W. John Albery.
Evolution of Enzyme Function and the Development of Catalytic Efficiency: Triosephosphate Isomerase, Jeremy R. Knowles, and W. John Albery.
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酶功能的进化和催化效率的发展：磷酸丙糖异构酶。Knowles和W.约翰·阿尔伯里
DOI：
10.1021/acs.biochem.1c00211
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发表时间：
2021-11-23
期刊：
影响因子：
2.9
通讯作者：
Gerlt, John A.
中科院分区：
文献类型：
--
作者：
Gerlt, John A.
每个读者都知道，一种酶通过降低激活能垒来加快反应的速度。然而，理解这一点是如何通过酶的结构及其与稳定络合物和过渡态的相互作用实现的，然后利用这一点来(重新)设计酶来催化新的反应，仍然是机械酶学的“圣杯”。必要的基础是自由能分布，它规定了束缚亚态、产物和中间体的能量，以及它们相互转化的过渡态。当将这一自由能分布与非催化反应的自由能分布相比较时，就可以确定建立和加强催化的策略。这一观点提醒读者，为酶催化反应确定的第一个自由能谱，即磷酸丙糖异构酶，于1976年由Jeremy R.Knowles，W.John Alberg和他的同事发表在《生物化学》杂志上。他们利用这一分布提出了三个步骤，即增加“微妙”，这可能会受到进化压力的影响，以增加通过反应坐标的通量：1)底物、产物和中间体的“均匀结合”；2)络合物的“差异结合”，使这些都是等能的(以最小化中间过渡态的能量)；以及3)“基本步骤的催化”，其中动力学上重要的化学步骤的过渡态被稳定，因此通量可以由底物结合或产物解离的速率来确定。这些论文继续指导酶催化反应的机理研究，并为新型酶的(重新)设计提供原则。
Every reader knows that an enzyme accelerates the rate of a reaction by reducing the activation-energy barrier. However, understanding how this is achieved by the structure of the enzyme and its interactions with stable complexes and transition states and, then, using this to (re)design enzymes to catalyze novel reactions remains the “holy grail” of mechanistic enzymology. The necessary foundation is the free-energy profile that specifies the energies of the bound substate, product and intervening intermediates as well as the transition states by which they are interconverted. When this free-energy profile is compared to that for the uncatalyzed reaction, strategies for establishing and enhancing catalysis can be identified. This Perspective reminds readers that the first free-energy profile determined for an enzyme-catalyzed reaction, that for triosephosphate isomerase, was published in Biochemistry in 1976 by Jeremy R. Knowles, W. John Albery, and coworkers. They used the profile to propose three steps of increasing “subtlety” that can be influenced by evolutionary pressure to increase the flux through the reaction coordinate: 1) “uniform binding” of substrate, product, and intermediates; 2) “differential binding” of complexes so that these are isoenergetic (to minimize the energy of the intervening transition states); and 3) “catalysis of an elementary step” in which the transition state for the kinetically significant chemical step is stabilized so that flux can be determined by the rate of substrate binding or product dissociation. These papers continue to guide mechanistic studies of enzyme-catalyzed reactions as well as provide principles for the (re)design of novel enzymes.
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影响因子：
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作者：
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