Abstract
The relative positions and conformations of the prosthetic group FAD and the cofactor NADH have been remarkably conserved within the structurally diverse group of flavin enzymes. To provide a chemical rational for such an obviously optimal relative disposition of the redox partners for efficient reaction we have synthesized NADH models with Zn(II)-cyclen substituents for reversible flavin binding ...
Abstract
The relative positions and conformations of the prosthetic group FAD and the cofactor NADH have been remarkably conserved within the structurally diverse group of flavin enzymes. To provide a chemical rational for such an obviously optimal relative disposition of the redox partners for efficient reaction we have synthesized NADH models with Zn(II)-cyclen substituents for reversible flavin binding in water. Altogether, four of these model systems with systematically varying spacer length between the recognition site and the redox active dihydronicotinamide were prepared. The binding of these model systems to riboflavin tetraacetate was confirmed by potentiometric pH titration in water and their reaction with flavin was followed by UV-vis spectroscopy in aqueous media under physiological conditions. The measurements reveal a significant rate enhancement of up to 175 times that of an intermolecular reaction. Moreover, a strong dependence of the reaction rate on the spacer length was observed, which clearly shows that within the dynamic reversible assembly only the optimal relative disposition of the redox partners ensures an efficient redox reaction.
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