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Cryo‐kinetics reveal dynamic effects on the chemistry of human dihydrofolate reductase

Adesina, Aduragbemi S., Luk, Louis Y. P. and Allemann, Rudolf K. 2021. Cryo‐kinetics reveal dynamic effects on the chemistry of human dihydrofolate reductase. ChemBioChem 10.1002/cbic.202100017

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Abstract

The results of cryo‐measurements of the kinetics of the human dihydrofolate reductase (HsDHFR) catalyzed reaction and the effects of protein motion on catalysis are reported. Isotopic enzyme labeling revealed an enzyme KIE (kHLE/kHHE) close to unity above 0 °C; however, the enzyme KIE was increased to 1.72±0.15 at −20 °C, indicating that the coupling of protein motions to the chemical step is minimized under optimal conditions but enhanced at non‐physiological temperatures.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Chemistry
Publisher: Wiley
ISSN: 1439-4227
Funders: BBSRC, Cardiff University
Date of First Compliant Deposit: 6 May 2021
Date of Acceptance: 19 April 2021
Last Modified: 24 May 2021 12:11
URI: http://orca.cf.ac.uk/id/eprint/140976

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