An alternative explanation for the catalytic proficiency of orotidine 5'-phosphate decarboxylase.
An alternative explanation for the catalytic proficiency of orotidine 5'-phosphate decarboxylase.
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DOI：
10.1021/ja011096f
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发表时间：
2001-12
影响因子：
15
通讯作者：
T. Lee;L. Chong;J. Chodera;P. Kollman
中科院分区：
文献类型：
--
作者：
T. Lee;L. Chong;J. Chodera;P. Kollman
乳清酸核苷5 '-磷酸脱羧酶（ODCase）是已知的最有效的酶，将乳清酸核苷5'-磷酸（OMP）的脱羧速率提高10倍（17），这对应于约24 kcal/mol的Δ Δ G ++。通过局部静电应力的基态不稳定最近已被提出作为催化速率增强的机制，这是在解决方案中相同的基础。我们已经进行了气相从头算量子力学计算结合自由能方法，连续溶剂模型，和分子动力学模拟，以评估替代机制。虽然我们不能再现实验观察到的DeltaDeltaG++定量，我们提出的证据表明，这DeltaDeltaG++是非常大的，在实验发现的范围内。因此，我们得出结论，优选的机制可能是不同的，在解决方案中，涉及平衡预质子化的OMP C5的催化赖氨酸残基，大大降低了障碍，随后的脱羧。
Orotidine 5'-phosphate decarboxylase (ODCase) is the most proficient enzyme known, enhancing the rate of decarboxylation of orotidine 5'-phosphate (OMP) by a factor of 10(17), which corresponds to a DeltaDeltaG++ of approximately 24 kcal/mol. Ground-state destabilization through local electrostatic stress has been recently proposed as the basis of catalytic rate enhancement for a mechanism that is the same as in solution. We have carried out gas-phase ab initio quantum mechanical calculations combined with a free energy method, a continuum solvent model, and molecular dynamics simulations to assess an alternative mechanism. Although we are not able to reproduce the experimentally observed DeltaDeltaG++ quantitatively, we present evidence that this DeltaDeltaG++ is very large, in the range found experimentally. We thus conclude that the preferred mechanism may well be different from that in solution, involving an equilibrium pre-protonation of OMP C5 by a catalytic lysine residue that greatly reduces the barrier to subsequent decarboxylation.