RESUMEN
Glutathione peroxidase, the first example of selenoproteins identified in mammals, was subjected to force field calculations and molecular dynamics in order to enable a clearer comprehension of enzymatic selenium catalysis. Starting from the established X-ray structure of bovine GPX, all kinetically defined intermediates and enzyme substrate complexes were modelled. The models thus obtained support the hypothesis that the essential steps of the catalysis are three distinct redox changes of the active site selenium which, in the ground state, presents itself at the surface of selenoperoxidases as the center of a characteristic triad built by selenocysteine, glutamine and tryptophan. In GPX, four arginine residues and a lysine residue provide an electrostatic architecture which, in each reductive step, directs the donor substrate GSH towards the catalytic center in such a way that its sulfhydryl group must react with the selenium moiety. To this end, different equally efficient modes of substrate binding appear possible. The models are consistent with substrate specificity data, kinetic pattern and other functional characteristics of the enzyme. Comparison of molecular models of GPX with those of other members of the GPX superfamily reveals that the cosubstrate binding mechanisms are unique for the classical type of cytosolic glutathione peroxidases but cannot operate e. g. in plasma GPX and phospholipid hydroperoxide GPX. The structural differences between the selenoperoxidases, shown to be relevant to their specificities, are discussed in terms of functional diversification within the GPX superfamily.
Asunto(s)
Glutatión Peroxidasa/metabolismo , Animales , Catálisis , Simulación por Computador , Humanos , Modelos MolecularesRESUMEN
An antifungal activity against Mucor hiemalis was detected in the culture broth of Sorangium cellulosum (Myxococcales) strain So ce90. The activity was excreted into the supernatant during the log and early stationary phase. When the adsorber resin XAD-16 was added to the culture, the active metabolites were quantitatively bound to the resin. The epothilons showed a high cytotoxicity for animal cells and mimic the biological effects of taxol (BOLLAG et al., Cancer Res. 55: 2325 approximately 2333, 1995).
Asunto(s)
Antifúngicos/química , Antifúngicos/aislamiento & purificación , Epotilonas , Compuestos Epoxi/aislamiento & purificación , Tiazoles/aislamiento & purificación , Animales , Antifúngicos/farmacología , Compuestos Epoxi/química , Compuestos Epoxi/farmacología , Fermentación , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Myxococcales , Tiazoles/química , Tiazoles/farmacología , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
An antifungal activity was detected in the culture broth of Sorangium cellulosum (Myxococcales), strain So ce26. The activity was excreted into the supernatant during the log and early stationary phase. The active substance was quantitatively bound to XAD absorber resin added to the medium at the beginning of the fermentation. The new secondary metabolite was called soraphen and is of special interest to plant disease control for its inhibitory activity against numerous phytopathogenic fungi.
Asunto(s)
Antifúngicos/aislamiento & purificación , Compuestos Heterocíclicos/aislamiento & purificación , Macrólidos , Myxococcales/metabolismo , Antifúngicos/análisis , Antifúngicos/farmacología , Recuento de Células , Cromatografía Líquida de Alta Presión , Fermentación , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacología , Pruebas de Sensibilidad Microbiana , Saccharomyces cerevisiae/efectos de los fármacos , TemperaturaRESUMEN
Myxochelin A, a new catechole siderophore, was isolated from the culture broth of the myxobacterium, Angiococcus disciformis strain An d30. As is the case with other iron-chelating compounds the production of myxochelin A could be markedly increased up to 44 mg/liter by fermentation at low iron concentrations (10(-7) M FeCl3). The new substance showed weak activity against some bacteria.