@article{826737e2428c49f0b8795837f4a684a7,
title = "Kemp Eliminases of the AlleyCat Family Possess High Substrate Promiscuity",
abstract = " 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 immunosuppressor 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 a .",
keywords = "Kemp elimination, Nuclear Magnetic Resonance, allostery, calmodulin, protein design",
author = "Caselle, {Elizabeth A.} and Yoon, {Jennifer H.} and Sagar Bhattacharya and Rempillo, {Joel J.L.} and Zs{\'o}fia Lengyel and Areetha D'Souza and Moroz, {Yurii S.} and Tolbert, {Patricia L.} and Volkov, {Alexander N.} and Marcello Forconi and Casta{\~n}eda, {Carlos A.} and Makhlynets, {Olga V.} and Korendovych, {Ivan V.}",
note = "Funding Information: We thank Prof. Dr. Patrick J. Bednarsky (University of Greifswald) for bringing chemical similarity of benzisoxazoles and leflunomide to our attention. The plasmid encoding the tKSI (Comamonas testosteroni) D38N gene was a generous gift from the Herschlag lab (Stanford University). This work was supported by the NIH (grants GM119634, RR016461, OD012254 and GM103499), the NSF (grants 1332349, 1750462 and 1229559), the College of Charleston [Summer Undergraduate Research with Faculty grants], the Howard Hughes Medical Institute [grant 52007537 through the Pre-college & Undergraduate Science Education Program], the Ralph E. Powe Junior Enhancement Awards to C.A.C. and I.V.K., the Nappi Family Award and the Alexander von Humboldt Foundation to I.V.K.> Publisher Copyright: {\textcopyright} 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim",
year = "2019",
month = mar,
day = "6",
doi = "10.1002/cctc.201801994",
language = "English (US)",
volume = "11",
pages = "1425--1430",
journal = "ChemCatChem",
issn = "1867-3880",
publisher = "Wiley - VCH Verlag GmbH & CO. KGaA",
number = "5",
}