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Behiry EM, Ruiz-Pernia JJ, Luk L, et al. Isotope Substitution of Promiscuous Alcohol Dehydrogenase Reveals the Origin of Substrate Preference in the Transition State. Angew Chem Int Ed Engl. 2018;57(12):3128-3131doi: 10.1002/anie.201712826.
Behiry, E. M., Ruiz-Pernia, J. J., Luk, L., Tuñón, I., Moliner, V., & Allemann, R. K. (2018). Isotope Substitution of Promiscuous Alcohol Dehydrogenase Reveals the Origin of Substrate Preference in the Transition State. Angewandte Chemie (International ed. in English), 57(12), 3128-3131. https://doi.org/10.1002/anie.201712826
Behiry, Enas M, et al. "Isotope Substitution of Promiscuous Alcohol Dehydrogenase Reveals the Origin of Substrate Preference in the Transition State." Angewandte Chemie (International ed. in English) vol. 57,12 (2018): 3128-3131. doi: https://doi.org/10.1002/anie.201712826
Behiry EM, Ruiz-Pernia JJ, Luk L, Tuñón I, Moliner V, Allemann RK. Isotope Substitution of Promiscuous Alcohol Dehydrogenase Reveals the Origin of Substrate Preference in the Transition State. Angew Chem Int Ed Engl. 2018 Mar 12;57(12):3128-3131. doi: 10.1002/anie.201712826. Epub 2018 Feb 19. PMID: 29341402; PMCID: PMC5861672.
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Angew Chem Int Ed Engl. 2018 Mar 12;57(12):3128-3131. doi: 10.1002/anie.201712826. Epub 2018 Feb 19.

Isotope Substitution of Promiscuous Alcohol Dehydrogenase Reveals the Origin of Substrate Preference in the Transition State.

Angewandte Chemie (International ed. in English)

Enas M Behiry, J Javier Ruiz-Pernia, Louis Luk, Iñaki Tuñón, Vicent Moliner, Rudolf K Allemann

Affiliations

  1. School of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT, UK.
  2. Departament de Química Física, Universitat de València, 46100, Burjassot, Spain.
  3. Departament de Química Física i Analítica, Universitat Jaume I, 12071, Castelló, Spain.

PMID: 29341402 PMCID: PMC5861672 DOI: 10.1002/anie.201712826

Abstract

The origin of substrate preference in promiscuous enzymes was investigated by enzyme isotope labelling of the alcohol dehydrogenase from Geobacillus stearothermophilus (BsADH). At physiological temperature, protein dynamic coupling to the reaction coordinate was insignificant. However, the extent of dynamic coupling was highly substrate-dependent at lower temperatures. For benzyl alcohol, an enzyme isotope effect larger than unity was observed, whereas the enzyme isotope effect was close to unity for isopropanol. Frequency motion analysis on the transition states revealed that residues surrounding the active site undergo substantial displacement during catalysis for sterically bulky alcohols. BsADH prefers smaller substrates, which cause less protein friction along the reaction coordinate and reduced frequencies of dynamic recrossing. This hypothesis allows a prediction of the trend of enzyme isotope effects for a wide variety of substrates.

© 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Keywords: alcohol dehydrogenase; enzyme catalysis; enzyme models; enzymes; isotope effects

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