Hyperconjugation Promotes Catalysis in a Pyridoxal 5′-Phosphate-Dependent Enzyme

• Published in: ACS catalysis Vol. 8; no. 7; pp. 6733 - 6737
• Main Authors: Dajnowicz, Steven, Parks, Jerry M, Hu, Xiche, Johnston, Ryne C, Kovalevsky, Andrey Y, Mueser, Timothy C
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 06.07.2018; American Chemical Society (ACS)
• Subjects: BASIC BIOLOGICAL SCIENCES; Biocatalysis; Hyperconjugation; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Natural Bond Orbitals; Quantum Chemistry; Vitamin B6; quantum chemistry; vitamin B6; hyperconjugation; biocatalysis; natural bond orbitals
• ISSN: 2155-5435; 2155-5435
• DOI: 10.1021/acscatal.8b01911

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. 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.