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

doi:10.1002/cctc.201801994

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 journal › Article › peer-review

3 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 language	English (US)
Pages (from-to)	1425-1430
Number of pages	6
Journal	ChemCatChem
Volume	11
Issue number	5
DOIs	https://doi.org/10.1002/cctc.201801994
State	Published - 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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10.1002/cctc.201801994

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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.}",

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year = "2019",

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doi = "10.1002/cctc.201801994",

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AU - Caselle, Elizabeth A.

AU - Yoon, Jennifer H.

AU - Bhattacharya, Sagar

AU - Rempillo, Joel J.L.

AU - Lengyel, Zsófia

AU - D'Souza, Areetha

AU - Moroz, Yurii S.

AU - Tolbert, Patricia L.

AU - Volkov, Alexander N.

AU - Forconi, Marcello

AU - Castañeda, Carlos A.

AU - Makhlynets, Olga V.

AU - Korendovych, Ivan V.

PY - 2019/3/6

Y1 - 2019/3/6

N2 - 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 .

AB - 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 .

KW - Kemp elimination

KW - Nuclear Magnetic Resonance

KW - allostery

KW - calmodulin

KW - protein design

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Kemp Eliminases of the AlleyCat Family Possess High Substrate Promiscuity

Abstract

Keywords

ASJC Scopus subject areas

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