Caselle Elizabeth A, Yoon Jennifer H, Bhattacharya Sagar, Rempillo Joel J L, Lengyel Zsófia, D'Souza Areetha, Moroz Yurii S, Tolbert Patricia L, Volkov Alexander N, Forconi Marcello, Castañeda Carlos A, Makhlynets Olga V, Korendovych Ivan V
Department of Chemistry, Syracuse University, 111 College Place, Syracuse, NY 13244, USA.
Department of Chemistry, Taras Shevchenko National University of Kyiv, 64 Volodymyrska St., Kyiv 01601, Ukraine.
ChemCatChem. 2019 Mar 6;11(5):1425-1430. doi: 10.1002/cctc.201801994. Epub 2019 Jan 15.
Minimalist enzymes designed to catalyze model reactions provide useful starting points for creating catalysts for practically important chemical transformations. We have shown that Kemp eliminases of the AlleyCat family facilitate conversion of leflunomide (an immunosupressor pro-drug) to its active form teriflunomide with outstanding rate enhancement (nearly four orders of magnitude) and catalytic proficiency (more than seven orders of magnitude) without any additional optimization. This remarkable activity is achieved by properly positioning the substrate in close proximity to the catalytic glutamate with very high pK.
设计用于催化模型反应的简约型酶为创建用于实际重要化学转化的催化剂提供了有用的起点。我们已经表明，AlleyCat家族的肯普消除酶能促进来氟米特（一种免疫抑制剂前药）转化为其活性形式特立氟胺，具有显著的速率增强（近四个数量级）和催化效率（超过七个数量级），且无需任何额外优化。这种显著的活性是通过将底物与具有非常高pK值的催化性谷氨酸紧密相邻地正确定位来实现的。
