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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.