skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: 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:
 [1]; ORCiD logo [2];  [3]; ORCiD logo [2]; ORCiD logo [4];  [3]
  1. Univ. of Toledo, OH (United States). Dept. of Chemistry and Biochemistry; Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Neutron Scattering Division
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). UT/ORNL Center for Molecular Biophysics, Biosciences Division
  3. Univ. of Toledo, OH (United States). Dept. of Chemistry and Biochemistry
  4. 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:
Journal Article: 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. doi: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. doi:10.1021/acscatal.8b01911.
@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}
}

Journal Article:
Free Publicly Available Full Text
This content will become publicly available on June 21, 2019
Publisher's Version of Record

Save / Share: