Kemp Eliminases of the AlleyCat Family Possess High Substrate Promiscuity

Elizabeth A. Caselle, Jennifer H. Yoon, Sagar Bhattacharya, Joel J.L. Rempillo, Zsófia Lengyel, Areetha D'Souza, Yurii S. Moroz, Patricia L. Tolbert, Alexander N. Volkov, Marcello Forconi, Carlos A. Castañeda, Olga V. Makhlynets, Ivan V. Korendovych

Research output: Contribution to journalArticle

1 Scopus citations

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 .

Original languageEnglish (US)
Pages (from-to)1425-1430
Number of pages6
JournalChemCatChem
Volume11
Issue number5
DOIs
StatePublished - Mar 6 2019

Keywords

  • Kemp elimination
  • Nuclear Magnetic Resonance
  • allostery
  • calmodulin
  • protein design

ASJC Scopus subject areas

  • Catalysis
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Caselle, E. A., Yoon, J. H., Bhattacharya, S., Rempillo, J. J. L., Lengyel, Z., D'Souza, A., Moroz, Y. S., Tolbert, P. L., Volkov, A. N., Forconi, M., Castañeda, C. A., Makhlynets, O. V., & Korendovych, I. V. (2019). Kemp Eliminases of the AlleyCat Family Possess High Substrate Promiscuity. ChemCatChem, 11(5), 1425-1430. https://doi.org/10.1002/cctc.201801994