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Abstract
Understanding how enzyme catalysis varies with temperature is key to
understanding catalysis itself and, ultimately, how to tune temperature
optima. Temperature dependence studies inform on the change in heat
capacity during the reaction, ΔCP‡,
and we have recently demonstrated that this can expose links between
the protein free energy landscape and enzyme turnover. By quantifying ΔCP‡,
we capture information on the changes to the distribution of
vibrational frequencies during enzyme turnover. The primary experimental
tool to probe the role of vibrational modes in a chemical/biological
process is isotope effect measurements, since isotopic substitution
primarily affects the frequency of vibrational modes at/local to the
position of isotopic substitution. We have monitored the temperature
dependence of a range of isotope effects on the turnover of a
hyper-thermophilic glucose dehydrogenase. We find a progressive effect
on the magnitude of ΔCP‡ with increasing isotopic substitution of d-glucose.
Our experimental findings, combined with molecular dynamics simulations
and quantum mechanical calculations, demonstrate that ΔCP‡ is sensitive to isotopic substitution. The magnitude of the change in ΔCP‡
due to substrate isotopic substitution indicates that small changes in
substrate vibrational modes are “translated” into relatively large
changes in the (distribution and/or magnitude of) enzyme vibrational
modes along the reaction. Therefore, the data suggest that relatively
small substrate isotopic changes are causing a significant change in the
temperature dependence of enzymatic rates.
Original language | English |
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Pages (from-to) | 5340-5349 |
Number of pages | 10 |
Journal | ACS Catalysis |
Volume | 8 |
Early online date | 25 Apr 2018 |
DOIs | |
Publication status | Published - 28 Apr 2018 |
Keywords
- Heat capacity
- isotope effect
- enzyme
- catalysis
- temperature dependence
Fingerprint
Dive into the research topics of 'Uncovering the Relationship between the Change in Heat Capacity for Enzyme Catalysis and Vibrational Frequency through Isotope Effect Studies'. Together they form a unique fingerprint.Projects
- 1 Finished
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Multi-scale enzyme modelling for SynBio: optimizing biocatalysts for selective synthesis of bioactive compounds
Van der Kamp, M. W. (Principal Investigator)
1/12/15 → 31/05/21
Project: Research