Journal article
Evolution of the Chemical Step in Enzyme Catalysis
ACS catalysis, Vol.11(11), pp.6726-6732
06/04/2021
DOI: 10.1021/acscatal.1c00442
Abstract
Enzymes have evolved to increase chemical reaction rates, some by factors exceeding the trillions, thus enabling the remarkable success of life on Earth. A typical enzymatic process includes substrate binding, a chemical step involving covalent bond rearrangements, and product release. A distinct energy threshold must be overcome for each of these steps to proceed. Past studies of enzyme evolution have focused on how the overall catalytic process or specific steps such as binding respond to selective pressures, but researchers have not deliberately monitored the evolution of the chemical step per se until now. To study the chemical step, we measured the temperature dependence of intrinsic kinetic isotope effects of dihydrofolate reductase from primitive to evolved variants. We found a progressive decrease in the temperature dependence of intrinsic kinetic isotope effects with evolution, indicating gradual narrowing of the thermally averaged donor-acceptor distance for hydride transfer in step with an increased catalytic efficiency. The important role played by residues that are remote from the active site in optimizing the chemical step of this complex, multistep enzymatic pathway is particularly notable.
Details
- Title: Subtitle
- Evolution of the Chemical Step in Enzyme Catalysis
- Creators
- Priyanka Singh - Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, United StatesAn Vandemeulebroucke - Laboratory of Organic Chemistry, ETH Zurich, 8093 Zurich, SwitzerlandJiayue Li - Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, United StatesCindy Schulenburg - Laboratory of Organic Chemistry, ETH Zurich, 8093 Zurich, SwitzerlandGabriel Fortunato - Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, United StatesAmnon Kohen - Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, United StatesDonald Hilvert - Laboratory of Organic Chemistry, ETH Zurich, 8093 Zurich, SwitzerlandChristopher M Cheatum - Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, United States
- Resource Type
- Journal article
- Publication Details
- ACS catalysis, Vol.11(11), pp.6726-6732
- DOI
- 10.1021/acscatal.1c00442
- ISSN
- 2155-5435
- eISSN
- 2155-5435
- Grant note
- DOI: 10.13039/501100003006, name: Eidgen?ssische Technische Hochschule Z?rich; DOI: 10.13039/501100001711, name: Schweizerischer Nationalfonds zur F?rderung der Wissenschaftlichen Forschung; DOI: 10.13039/100000001, name: National Science Foundation, award: CHE-1707598
- Language
- English
- Date published
- 06/04/2021
- Academic Unit
- Liberal Arts and Science Admin; Chemistry
- Record Identifier
- 9984217451902771
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