Hyperconjugation Promotes Catalysis in a Pyridoxal 5'-Phosphate-Dependent Enzyme
Abstract
Pyridoxal 5'-phosphate (PLP)-dependent enzymes facilitate reaction specificity by aligning the scissile σ-bond of the PLP-substrate covalent complex perpendicular to the ring of the cofactor. Current models propose that this alignment causes a destabilization of the ground state. To test this hypothesis, quantum chemical calculations, utilizing our recent neutron diffraction models of aspartate aminotransferase, were performed. The calculations reveal that the scissile σ-bond orbital overlaps significantly with the π* orbital of the Schiff base. Here, this σ → π* hyperconjugation interaction stabilizes the ground state of the external aldimine and substantially contributes to transition-state stabilization by withdrawing electron density from the Cα-H σ bond into the π system of PLP, enhancing the rate of catalysis.
- Authors:
-
[2];
[2];
[4];
- Univ. of Toledo, OH (United States). Dept. of Chemistry and Biochemistry; Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Neutron Scattering Division
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). UT/ORNL Center for Molecular Biophysics, Biosciences Division
- Univ. of Toledo, OH (United States). Dept. of Chemistry and Biochemistry
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Neutron Scattering Division
- Publication Date:
- Research Org.:
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1459276
- Grant/Contract Number:
- AC05-00OR22725
- Resource Type:
- Accepted Manuscript
- Journal Name:
- ACS Catalysis
- Additional Journal Information:
- Journal Volume: 8; Journal Issue: 7; Journal ID: ISSN 2155-5435
- Publisher:
- American Chemical Society (ACS)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; Biocatalysis; Quantum Chemistry; Vitamin B6; Natural Bond Orbitals; Hyperconjugation
Citation Formats
Dajnowicz, Steven, Parks, Jerry M., Hu, Xiche, Johnston, Ryne C., Kovalevsky, Andrey Y., and Mueser, Timothy C. Hyperconjugation Promotes Catalysis in a Pyridoxal 5'-Phosphate-Dependent Enzyme. United States: N. p., 2018.
Web. doi:10.1021/acscatal.8b01911.
Dajnowicz, Steven, Parks, Jerry M., Hu, Xiche, Johnston, Ryne C., Kovalevsky, Andrey Y., & Mueser, Timothy C. Hyperconjugation Promotes Catalysis in a Pyridoxal 5'-Phosphate-Dependent Enzyme. United States. https://doi.org/10.1021/acscatal.8b01911
Dajnowicz, Steven, Parks, Jerry M., Hu, Xiche, Johnston, Ryne C., Kovalevsky, Andrey Y., and Mueser, Timothy C. Thu .
"Hyperconjugation Promotes Catalysis in a Pyridoxal 5'-Phosphate-Dependent Enzyme". United States. https://doi.org/10.1021/acscatal.8b01911. https://www.osti.gov/servlets/purl/1459276.
@article{osti_1459276,
title = {Hyperconjugation Promotes Catalysis in a Pyridoxal 5'-Phosphate-Dependent Enzyme},
author = {Dajnowicz, Steven and Parks, Jerry M. and Hu, Xiche and Johnston, Ryne C. and Kovalevsky, Andrey Y. and Mueser, Timothy C.},
abstractNote = {Pyridoxal 5'-phosphate (PLP)-dependent enzymes facilitate reaction specificity by aligning the scissile σ-bond of the PLP-substrate covalent complex perpendicular to the ring of the cofactor. Current models propose that this alignment causes a destabilization of the ground state. To test this hypothesis, quantum chemical calculations, utilizing our recent neutron diffraction models of aspartate aminotransferase, were performed. The calculations reveal that the scissile σ-bond orbital overlaps significantly with the π* orbital of the Schiff base. Here, this σ → π* hyperconjugation interaction stabilizes the ground state of the external aldimine and substantially contributes to transition-state stabilization by withdrawing electron density from the Cα-H σ bond into the π system of PLP, enhancing the rate of catalysis.},
doi = {10.1021/acscatal.8b01911},
journal = {ACS Catalysis},
number = 7,
volume = 8,
place = {United States},
year = {Thu Jun 21 00:00:00 EDT 2018},
month = {Thu Jun 21 00:00:00 EDT 2018}
}
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Figures / Tables:
Figure 1: Active site pre-organization in AAT. (A) Active site of AAT in the external aldimine state. Green = large domain; Cyan = small domain. The arrow indicates potential rotation about the C$α$-NSB bond. (B) External aldimine with labels for atoms included in the torsional angle of interest. (C) Normalizedmore »
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Works referencing / citing this record:
Hyperconjugation promoted by hydrogen bonding between His98/His241 and a carboxyl group contributes to tyrosine decarboxylase catalysis
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