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 Castaneda, Olga Makhylnets, Ivan Korendovych

Research output: Contribution to journalArticle

1 Citation (Scopus)

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)
JournalChemCatChem
DOIs
StatePublished - Jan 1 2019

Fingerprint

leflunomide
Prodrugs
Glutamic Acid
Enzymes
glutamates
Catalysts
Substrates
positioning
proximity
enzymes
drugs
catalysts
optimization
augmentation
teriflunomide

Keywords

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

ASJC Scopus subject areas

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

Cite this

Caselle, E. A., Yoon, J. H., Bhattacharya, S., Rempillo, J. J. L., Lengyel, Z., D'Souza, A., ... Korendovych, I. (2019). Kemp Eliminases of the AlleyCat Family Possess High Substrate Promiscuity. ChemCatChem. https://doi.org/10.1002/cctc.201801994

Kemp Eliminases of the AlleyCat Family Possess High Substrate Promiscuity. / 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; Castaneda, Carlos; Makhylnets, Olga; Korendovych, Ivan.

In: ChemCatChem, 01.01.2019.

Research output: Contribution to journalArticle

Caselle, EA, Yoon, JH, Bhattacharya, S, Rempillo, JJL, Lengyel, Z, D'Souza, A, Moroz, YS, Tolbert, PL, Volkov, AN, Forconi, M, Castaneda, C, Makhylnets, O & Korendovych, I 2019, 'Kemp Eliminases of the AlleyCat Family Possess High Substrate Promiscuity', ChemCatChem. https://doi.org/10.1002/cctc.201801994
Caselle EA, Yoon JH, Bhattacharya S, Rempillo JJL, Lengyel Z, D'Souza A et al. Kemp Eliminases of the AlleyCat Family Possess High Substrate Promiscuity. ChemCatChem. 2019 Jan 1. https://doi.org/10.1002/cctc.201801994
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 ; Castaneda, Carlos ; Makhylnets, Olga ; Korendovych, Ivan. / Kemp Eliminases of the AlleyCat Family Possess High Substrate Promiscuity. In: ChemCatChem. 2019.
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