42212-75-9Relevant academic research and scientific papers
Stereochemical and isotopic labeling studies of 2-oxo-hept-4-ene-1,7- dioate hydratase: Evidence for an enzyme-catalyzed ketonization step in the hydration reaction
Burks, Elizabeth A.,Johnson Jr., William H.,Whitman, Christian P.
, p. 7665 - 7675 (1998)
2-Oxo-hept-4-ene-1,7-dioate hydratase from Escherichia coli C converts 2-oxo-hept-4-ene-1,7-dioate to 2-oxo-4-hydroxy-hepta-1,7-dioate by the addition of water using magnesium as a cofactor. The enzyme is one of a set of inducible enzymes, known collectively as the homoprotocatechuate meta- fission pathway. The entire pathway enables the organism to utilize aromatic amino acids as its sole sources of carbon and energy. Expression and purification of 2-oxo-hept-4-ene-1,7-dioate hydratase to homogeneity permitted kinetic, isotopic labeling, and stereochemical studies. Kinetic studies show that the enzyme processes either 2-oxo-hept-4-ene-1,7-dioate or 2-hydroxy-2,4-heptadiene-1,7-dioate to product with comparable facility. Isotope labeling studies show that the hydratase catalyzes the incorporation of a solvent deuteron at both C-3 and C-5 when the reaction is performed in 2H2O. The enzyme also accelerates the exchange of the C-3 proton of the alternate substrate 2-oxo-1,7-heptadioate with solvent deuterons. The results are consistent with a mechanism in which the enzyme catalyzes the isomerization of 2-oxo-hept-4-ene-1,7-dioate to its α,β-unsaturated ketone followed by the Michael addition of water. Whether this mechanistic sequence involves a one-base or a two-base mechanism is not yet known.
Design, synthesis, and evaluation of 6-carboxyalkyl and 6-phosphonoxyalkyl derivatives of 7-oxo-8-ribitylaminolumazines as inhibitors of riboflavin synthase and lumazine synthase
Cushman, Mark,Yang, Donglai,Gerhardt, Stefan,Huber, Robert,Fischer, Markus,Kis, Klaus,Bacher, Adelbert
, p. 5807 - 5816 (2007/10/03)
A series of 6-carboxyalkyl and 6-phosphonoxyalkyl derivatives of 7-oxo-8-D-ribityllumazine were synthesized as inhibitors of both Escherichia coli riboflavin synthase and Bacillus subtilis lumazine synthase. The compounds were designed to bind to both the ribitylpurine binding site and the phosphate binding site of lumazine synthase. In the carboxyalkyl series, maximum activity against both enzymes was observed with the 3′-carboxypropyl compound 22. Lengthening or shortening the chain linking the carboxyl group to the lumazine by one carbon resulted in decreased activity. In the phosphonoxyalkyl series, the 3′-phosphonoxypropyl compound 33 was more potent than the 4′-phosphonoxybutyl derivative 39 against lumazine synthase, but it was less potent against riboflavin synthase. Molecular modeling suggested that the terminal carboxyl group of 6-(3′-carboxypropyl)-7-oxo-8-D-ribityllumazine (22) may bind to the side chains of Arg127 and Lys135 of the enzyme. A hypothetical molecular model was also constructed for the binding of 6-(2′-carboxyethyl)-7-oxolumazine (15) in the active site of E. coli riboflavin synthase, which demonstrated that the active site could readily accommodate two molecules of the inhibitor.
