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Kemp Eliminases of the AlleyCat Family Possess High Substrate Promiscuity
Author(s) -
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.
Publication year - 2019
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201801994
Subject(s) - substrate (aquarium) , catalysis , leflunomide , chemistry , combinatorial chemistry , active site , enzyme , stereochemistry , biophysics , biochemistry , biology , ecology , methotrexate , immunology
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 .