Journal article
Protein Mass Effects on Formate Dehydrogenase
Journal of the American Chemical Society, Vol.139(48), pp.17405-17413
2017
DOI: 10.1021/jacs.7b08359
PMCID: PMC5800309
PMID: 29083897
Abstract
Isotopically labeled enzymes (denoted as "heavy" or "Born-Oppenheimer" enzymes) have been used to test the role of protein dynamics in catalysis. The original idea was that the protein's higher mass would reduce the frequency of its normal-modes without altering its electrostatics. Heavy enzymes have been used to test if the vibrations in the native enzyme are coupled to the chemistry it catalyzes, and different studies have resulted in ambiguous findings. Here the temperature-dependence of intrinsic kinetic isotope effects of the enzyme formate dehydrogenase is used to examine the distribution of H-donor to H-acceptor distance as a function of the protein's mass. The protein dynamics are altered in the heavy enzyme to diminish motions that determine the transition state sampling in the native enzyme, in accordance with a Born-Oppenheimer-like effect on bond activation. Findings of this work suggest components related to fast frequencies that can be explained by Born-Oppenheimer enzyme hypothesis (vibrational) and also slower time scale events that are non-Born-Oppenheimer in nature (electrostatic), based on evaluations of protein mass dependence of donor-acceptor distance and forward commitment to catalysis along with steady state and single turnover measurements. Together, the findings suggest that the mass modulation affected both local, fast, protein vibrations associated with the catalyzed chemistry and the protein's macromolecular electrostatics at slower time scales; that is, both Born-Oppenheimer and non-Born-Oppenheimer effects are observed. Comparison to previous studies leads to the conclusion that isotopic labeling of the protein may have different effects on different systems, however, making heavy enzyme studies a very exciting technique for exploring the dynamics link to catalysis in proteins.
Details
- Title: Subtitle
- Protein Mass Effects on Formate Dehydrogenase
- Creators
- Chethya RanasingheQi GuoPaul J SapienzaAndrew L LeeDaniel M QuinnChristopher M CheatumAmnon Kohen
- Resource Type
- Journal article
- Publication Details
- Journal of the American Chemical Society, Vol.139(48), pp.17405-17413
- DOI
- 10.1021/jacs.7b08359
- PMID
- 29083897
- PMCID
- PMC5800309
- NLM abbreviation
- J Am Chem Soc
- ISSN
- 1520-5126
- eISSN
- 1520-5126
- Grant note
- DOI: 10.13039/100000165, name: Division of Chemistry, award: CHE-1149023; DOI: 10.13039/501100001742, name: United States-Israel Binational Science Foundation, award: BSF 2012340; DOI: 10.13039/100000057, name: National Institute of General Medical Sciences, award: GM065368, GM079368
- Language
- English
- Date published
- 2017
- Academic Unit
- Core Research Facilities; Chemistry
- Record Identifier
- 9983985832702771
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