6533b81ffe1ef96bd1277a78
RESEARCH PRODUCT
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subject
0301 basic medicinebiologyChemistryStereochemistrySubstrate (chemistry)Active siteGeneral Chemistry010402 general chemistry01 natural sciencesCatalysisTransition state0104 chemical sciencesEnzyme catalysisReaction coordinate03 medical and health scienceschemistry.chemical_compound030104 developmental biologyBenzyl alcoholKinetic isotope effectbiology.proteinAlcohol dehydrogenasedescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-02-19 | Angewandte Chemie International Edition |