Enzyme catalysis: over-the-barrier or through-the-barrier?
Enzyme catalysis: over-the-barrier or through-the-barrier?
复制标题
酶催化：越过屏障还是穿过屏障？
DOI：
10.1016/s0968-0004(00)01642-x
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发表时间：
2000
影响因子：
13.8
通讯作者：
Nigel S. Scrutton
中科院分区：
文献类型：
--
作者：
M. Sutcliffe;Nigel S. Scrutton
406如果将其作为粒子处理，则无法访问(图1B)。在量子世界中，从反应物到产物的路径可能不需要通过势垒，但可以通过量子隧道通过势垒。对于轻粒子(如电子)来说，量子隧道效应更为明显，因为粒子的波长与粒子质量的平方根成反比。量子隧道技术现在已经为生物电子转移奠定了坚实的基础，14并且可以在长达25-30埃的距离内进行。但其他粒子呢？氢(钚)核的质量是电子的1840倍。因此，钚的隧道距离为0.58？，其概率与电子隧道超过25？的概率相同。这个距离很小，但它的长度与反应坐标(即势垒的宽度)相似。这表明隧道作用可能在酶促氢转移中起重要作用。氢的同位素[即氢(D)和氚(T)]的质量和隧穿几率分别超过了0.41和0.34，与电子超过25ä的几率相同(对于氚，参看0.58ä)。与氢转移相比，D转移和T转移的可能性降低，这使得底物分子内的同位素替代成为检测化学反应和生物反应中氢隧道效应的一种有吸引力的手段15。Klinman和他的同事首先获得了与酶催化反应中的H隧道一致的实验证据，该证据基于动力学同位素效应与经典行为预期的偏差。自从他们提出了酵母酒精脱氢酶16在生理温度下的H隧道效应以来，他们在牛血清胺氧化酶17、单胺氧化酶18和葡萄糖氧化酶19中也表现出了类似的效果。这些系统中的隧穿用TST的静态势垒描述来描述，但是，H转移不是越过势垒，而是通过量子隧穿发生在势能面鞍点以下。最近，Klinman提出，在脂氧合酶催化的反应中，H和D的“纯”隧道作用(即底物不会爬上势垒)发生，这也被用TST20的“静态”势垒描述来解释。在后一种情况下，发现反应速率基本上与温度无关，从而产生了能垒是静态的而不是动态的假设。然而，正如经典的越界转移所讨论的那样，蛋白质动力学在生物催化中被认为是起主要作用的，它引起了一个“起伏的”势能面。因此，需要探索蛋白质动力学和量子隧道(称为振动辅助隧道)之间联系的可能性。
406 inaccessible if it were treated as a particle (Fig. 1b). In the quantum world, the pathway from reactants to products might not need to pass over the barrier but could pass through the barrier by quantum tunnelling. Quantum tunnelling is more pronounced for light particles (eg electrons), because the wavelength of a particle is inversely proportional to the square root of the mass of the particle. Quantum tunnelling is now firmly established for biological electron transfer14 and can take place over distances as large as 25–30 Å. But what about other particles? The mass of the hydrogen (ie protium) nucleus is 1840 times that of the electron. Protium can therefore tunnel over a distance of 0.58 Å with the same probability as an electron tunnelling over 25 Å. This distance is small, but it is similar in length to a reaction coordinate (ie width of a potential energy barrier). This suggests that tunnelling might be important in enzymatic H-transfer. Isotopes of hydrogen [ie deuterium (D) and tritium (T)] have increased mass and tunnel with the same probability over 0.41 Å and 0.34 Å, respectively, as an electron does over 25 Å (cf 0.58 Å for protium). The decreased probability of D-and T-transfer compared with H-transfer makes isotopic substitution within a substrate molecule an attractive means of detecting H-tunnelling in chemical and biological reactions15. Klinman and co-workers were the first to obtain experimental evidence consistent with H-tunnelling in an enzymecatalysed reaction on the basis of deviations in kinetic isotope effect from that expected for classical behaviour. Since their proposal of H-tunnelling at physiological temperatures in yeast alcohol dehydrogenase16, they have also demonstrated similar effects in bovine serum amine oxidase17, monoamine oxidase18 and glucose oxidase19. Tunnelling in these systems was described in terms of the ‘static’barrier depictions of TST, but, rather than passing over the barrier, H-transfer was envisaged to occur just below the saddlepoint of the potential energy surface by quantum tunnelling. More recently, Klinman has suggested that ‘pure’tunnelling (ie the substrate does not ascend the barrier) of H and D occurs in the reaction catalysed by lipooxygenase, and this too was interpreted using the ‘static’barrier depictions of TST20. In this latter case, the reaction rate was found to be essentially independent of temperature, giving rise to the assumption that the energy barrier is static rather than dynamic. However, as discussed for classical over-the-barrier transfers, protein dynamics, which give rise to a ‘fluctuating’potential energy surface, are envisaged to play a major role in biological catalysis. The possibility of a link between protein dynamics and quantum tunnelling (termed vibrationally assisted tunnelling) therefore needs to be explored.
黄素酶单胺氧化酶 B 中的氢隧道。
影响因子：
2.9
作者：
Jonsson,T;Edmondson,DE;Klinman,JP
通讯作者：
Klinman,JP
压力对酵母醇脱氢酶氘同位素效应的影响：催化机械模型的证据。
影响因子：
2.9
作者：
Northrop,DB;Cho,YK
通讯作者：
Cho,YK
影响因子：
2.9
作者：
Kohen, A;Jonsson, T;Klinman, JP
通讯作者：
Klinman, JP