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Evidence that a 'dynamic knockout' in Escherichia coli dihydrofolate reductase does not affect the chemical step of catalysis

Loveridge, Edric Joel, Behiry, Enas Mamdouh, Guo, Jian Nan and Allemann, Rudolf Konrad 2012. Evidence that a 'dynamic knockout' in Escherichia coli dihydrofolate reductase does not affect the chemical step of catalysis. Nature Chemistry 4 (4) , pp. 292-297. 10.1038/nchem.1296

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Abstract

The question of whether protein motions play a role in the chemical step of enzymatic catalysis has generated much controversy in recent years. Debate has recently reignited over possible dynamic contributions to catalysis in dihydrofolate reductase, following conflicting conclusions from studies of the N23PP/S148A variant of the Escherichia coli enzyme. By investigating the temperature dependence of kinetic isotope effects, we present evidence that the reduction in the hydride transfer rate constants in this variant is not a direct result of impairment of conformational fluctuations. Instead, the conformational state of the enzyme immediately before hydride transfer, which determines the electrostatic environment of the active site, affects the rate constant for the reaction. Although protein motions are clearly important for binding and release of substrates and products, there appears to be no detectable dynamic coupling of protein motions to the hydride transfer step itself.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Cardiff Catalysis Institute (CCI)
Chemistry
Subjects: Q Science > QD Chemistry
Publisher: Nature Publishing Group
ISSN: 1755-4330
Funders: BBSRC
Last Modified: 05 Jun 2017 03:08
URI: http://orca.cf.ac.uk/id/eprint/26043

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Cited 32 times in Web of Science. View in Web of Science.

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