Lee J K, Houk K N
Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA.
Science. 1997 May 9;276(5314):942-5. doi: 10.1126/science.276.5314.942.
A mechanism is proposed to explain the activity of orotidine 5'-monophosphate decarboxylase (ODCase). This enzyme is the one of the most proficient known, with a catalytic proficiency (kcat/Km)/knon = 10(23) M-1. Quantum mechanical calculations predict a mechanism involving a stabilized carbene intermediate, which represents a previously unrecognized mode of enzymatic activity for ODCase. The proposed mechanism involves proton transfer from a weak acid (pKa = 7, where Ka is the acid constant) concerted with decarboxylation, in a nonpolar enzyme environment. Such a mechanism makes possible different approaches to the design of ODCase inhibitors. Furthermore, the prediction that general acid catalysis may only be effective in low dielectric media is of general significance for understanding the activity of many enzymes.
本文提出了一种机制来解释乳清苷5'-单磷酸脱羧酶（ODCase）的活性。该酶是已知最高效的酶之一，其催化效率（kcat/Km）/knon = 10(23) M-1。量子力学计算预测了一种涉及稳定卡宾中间体的机制，这代表了ODCase一种先前未被认识到的酶促活性模式。所提出的机制涉及在非极性酶环境中，质子从弱酸（pKa = 7，其中Ka是酸常数）转移并与脱羧反应协同进行。这种机制为ODCase抑制剂的设计提供了不同的方法。此外，关于一般酸催化可能仅在低介电介质中有效的预测，对于理解许多酶的活性具有普遍意义。
