Reductase activity protein

Vorontsov, 1.1., Minasov, G., Brunzelle, J.S., Shuvalova, L., Kir-yukhina, O., Collart, F.R., Anderson, W.F. (2007). Crystal stmcture of an apo form of Shigella flexneri ArsH protein with an NADPH-dependent FMN reductase activity. Protein Sci. 16 2483-90. 

The testes and adrenal glands produce 90% and 10%, respectively, of circulating testosterone. Testosterone enters prostate cells, where predominantly type II 5a-reductase activates testosterone to dihydrotestosterone, which combines with a cytoplasmic receptor. The complex enters the nucleus and induces changes in protein synthesis which promote glandular tissue growth of the prostate. Thus, 5a-reductase inhibitors (e.g., finasteride and dutas-teride) directly interfere with one of the major etiologic factors of BPH. 

The ent-fes-fep gene cluster is necessary for the synthesis of enterobactin and transport of the iron loaded siderophore. The fes gene product was shown to be necessary for utilization of the siderophore-bound iron inside the cell. The protein has an esterase activity which cleaves the ester bonds of the cyclic 2,3-dihydroxybenzoylserine ester in enterobactin. However, the esterase activity of Fes does not seem to be important for iron mobilization since Fes is also necessary for the utilization of iron from enterobactin analogues which do not have ester bonds (Heidinger et ah, 1983). No reductase activity has been found in Fes (Brickman and McIntosh, 1992) or in any other protein encoded in the ent-fes-fep gene cluster. 

There is some evidence that the iron-sulfur protein, FhuF, participates in the mobilization of iron from hydroxamate siderophores in E. coli (Muller et ah, 1998 Hantke, K. unpublished observations). However, a reductase activity of FhuF has not been demonstrated. Many siderophore-iron reductases have been shown to be active in vitro and some have been purified. The characterization of these reductases has revealed them to be flavin reductases which obtain the electrons for flavin reduction from NAD(P)H, and whose main functions are in areas other than reduction of ferric iron (e.g. flavin reductase Fre, sulfite reductase). To date, no specialized siderophore-iron reductases have been identified. It has been suggested that the reduced flavins from flavin oxidoreductases are the electron donors for ferric iron reduction (Fontecave et ah, 1994). Recently it has been shown, after a fruitless search for a reducing enzyme, that reduction of Co3+ in cobalamin is achieved by reduced flavin. Also in this case it was suggested that cobalamins and corrinoids are reduced in vivo by flavins which may be generated by the flavin... 

The microsome fractions see Fig. 1) that were prepared from mulberry cortical parenchyma cells were fractionated to 24 or 25 fractions using the 15-50% sucrose linear density gradient centrifugation see Fig. 2). Profiles of the marker enzymes and the protein content are described in Fig. 3. In general, the antimycin A-insensitive cytochrome c reductase activity is exhibited at a lower density than are those of the marker enzymes. The fraction that exhibited the highest antimycin A-insensitive cytochrome c reductase activity for each month was used as the ER-enriched fraction. 

These findings are at variance with reported increases in cytochrome P-450 content of rats fed increasing levels of casein (45, 46, 47, 49, 50). Only slight differences were observed in cytochrome c reductase activities between the diets, with the highest activity of 20nmoles cytochrome c reduced/min/mg protein occurring in fish fed the 32% casein diet (Table III). 

Some aspects of the proposed Rbr/Rbo oxidative stress defense system in D. vulgaris resemble those recently suggested for oxidative stress protection in the anaerobic hyperthermophilic archaeon Pyrococcus furiosus (Jenney et al. 1999). Pyrococcus furiosus contains an Nlr-like protein with superoxide reductase activity as well as an Rbr, the genes for which are tandemly located. The microorganismic segregation of SOD/catalase between aerobes and anaerobes appears to be less distinct than for Rbo/Rbr, which, as noted above, have so far been found only in air-sensitive microbes (Kirschvink et al. 2000). The latter segregation suggests that the Rbo/Rbr oxidative stress protection system is well suited to protection of anaerobic life in an aerobic world. 

The ferro-complex CD spectrum shows that reduction of the heme iron alters the heme environment. Redox-induced protein conformation changes could alter the S5unmetry in the heme pocket or produce two binding modes for the reduced complex whose asymmetries nearly cancel each other. Redox-linked conformational changes are especially interesting in view of recent findings of oxido-reductase activity associated with the heme-hemopexin-receptor interaction (89). 

There are a number of findings suggesting that agents that facilitate elimination of protein carbonyls (by either proteolytic elimination or by enzymically mediated chemical reduction) may suppress neurodegenerative conditions in model systems (Botella et al., 2004). Consequently, as carnosine may also react with protein carbonyls, it is theoretically possible that it could suppress formation and /the reactivity of protein carbonyls in the brain. Whether carnosine participates in carbonyl reductase activity has not been investigated but it is also a reasonable speculation. 

Dye oxidation (e.g., tetrazolium reductase activity with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, MTT 2-[4-iodophenyl]-3-[4-nitrophenyl]-5-[2,4-disulfophenyl]-2H tetrazolium monosodium salt, WST-1 3- (4,5 -carboxymethoxyphenyl) -2-(4-sulfophenyl)-2 H-tetra-zolium, MTS 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt, XTT 2,2 -di-p-nitrophenyl-5,5 -diphenyl-3,3 -(3,3 -dimethoxy-4,4 -diphe-nylenej-ditetrazolium chloride, NET), Alamar blue assays, ATP concentration (e.g., luciferase assay), oxygen consumption (e.g., oxygen electrodes, phosphorescent oxygen-sensitive dyes), mitochondrial protein and nucleic acid synthesis mitochondrial mass (e.g., mitotracker dyes) mitochondrial membrane potential (e.g., tetramethylrho-damine methyl ester, TMRM tetramethylrhodamine ethyl ester, TMRE)... 

Non-sex accessory tissues also are targets for the protein anabolic actions of androgens. These tissues possess lower levels of endogenous hormone, minimal 5a-reductase activity, and lower concentrations of specific androgen receptors. The protein anabolic actions are probably mediated by an interaction with the androgen receptor. 

Inhibitors of HMG-CoA reductase activity (for example compac-tin240), or compounds that lower the levels of the enzyme (including a number of oxygenated cholesterol derivatives,241- 24 la such as 25-liy-droxycholesterol), not only decrease the formation of polyprenyl diphosphate, but also affect the formation of cholesterol and the polyprenyl side-chains of coenzyme Q. Consequently, prolonged treatment with such compounds may cause side effects, for example, changes in membrane fluidity (see also, Section III,5), decreased activity of membrane enzymes,1214,2,3 and inactivation of membrane transport systems,246 and, therefore, indirectly prevent glvcosvlation of proteins. 

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