Enzyme Architecture: Activation of Phosphite Dehydrogenase-Catalyzed Hydride Transfer by NAD⁺ Cofactor Fragments.

ABSTRACT: We report the results of experiments to test the hypothesis that binding energy from the adenosine diphosphate (ADP) fragment of the NAD⁺ cofactor is utilized to drive a protein conformational change that activates phosphite dehydrogenase (PTDH) for catalysis of hydride transfer from phosphite to NAD⁺. The ADP fragment of the NAD⁺ cofactor provides >8.5 kcal/mol stabilization of the transition state for PTDH-catalyzed hydride transfer. The ADP and AMP fragments of NAD⁺ activate PTDH for catalysis of hydride transfer from phosphite to nicotinamide riboside (NR). At a 1.0 M standard state these activators stabilize the hydride transfer transition state by 5.1 (ADP) and 2.7 (AMP) kcal/mol, so the activation is due to protein interactions with both t

SUBMITTER: Hegazy R 

PROVIDER: S-EPMC12676663 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature