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Protein motions, dynamic effects and thermal stability in dihydrofolate reductase from the hyperthermophile thermotoga maritima

Allemann, Rudolf Konrad, Loveridge, Edric and Luk, Louis Yu Pan 2015. Protein motions, dynamic effects and thermal stability in dihydrofolate reductase from the hyperthermophile thermotoga maritima. In: Olivares-Quiroz, Luis, Guzmán-López, Orlando and Jardón-Valadez, Hector Eduardo eds. Physical Biology of Proteins and Peptides: Theory, Experiment, and Simulation, Springer International Publishing, pp. 99-113. (10.1007/978-3-319-21687-4_6)

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Abstract

Dihydrofolate reductase (DHFR) has long been used as a model system in studies of the relationship between enzyme structure and catalysis. DHFR from the hyperthermophilic bacterium Thermotoga maritima (TmDHFR) is substantially different to other chromosomal DHFRs. It is dimeric where most others are monomeric, it lacks the conformational behaviour of monomeric DHFRs, and the kinetics of the catalysed reaction are significantly different. Experimental and computational studies of TmDHFR and comparison to other DHFRs have yielded deep insights into the role of enzyme motions and dynamics in catalysis. Mutational studies and formation of hybrids between TmDHFR and a monomeric homologue have demonstrated that dimerisation is required for extreme thermostability, but also leads to an inability to adequately close the active site with detrimental effects for the speed of the catalysed reaction. However, in common with other DHFRs there is no involvement of large-scale enzyme motions in the chemical reaction itself and dynamic coupling to the reaction coordinate is efficiently minimised. Studies of DHFRs from hyperthermophilic organisms and comparisons to their mesophilic counterparts remain a rich source of information on the fundamental nature of enzyme catalysis.

Item Type: Book Section
Date Type: Publication
Status: Published
Schools: Chemistry
Subjects: Q Science > QD Chemistry
Publisher: Springer International Publishing
ISBN: 9783319216874
Last Modified: 05 Jun 2017 05:24
URI: http://orca.cf.ac.uk/id/eprint/86817

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