Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.6.99.3 (diaphorase)
5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cysteine desulfurase, IscS, provides sulfur for Fe-S cluster synthesis in vitro, but a role for IscS in in vivo Fe-S cluster formation has yet to be established. To study the in vivo function of IscS in Escherichia coli, a strain lacking IscS was constructed and characterized. Using this iscS deletion strain, we have observed decreased specific activities for proteins containing [4Fe-4S] clusters from soluble (aconitase B, 6-phosphogluconate dehydratase, glutamate synthase, fumarase A, and FNR) and membrane-bound proteins (NADH dehydrogenase I and succinate dehydrogenase). A specific role for IscS in in vivo Fe-S cluster assembly was demonstrated by showing that an Fe-S cluster independent mutant of FNR is unaffected by the lack of IscS. These data support the conclusion that, via its cysteine desulfurase activity, IscS provides the sulfur that subsequently becomes incorporated during in vivo Fe-S cluster synthesis. We also have characterized a growth phenotype associated with the loss of IscS. Under aerobic conditions the deletion of IscS caused an auxotrophy for thiamine and nicotinic acid, whereas under anaerobic conditions, only nicotinic acid was required. The lack of IscS also had a general effect on the growth of E. coli because the iscS deletion strain grew at half the rate of wild type in many types of media even when the auxotrophies were satisfied.
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PMID:The cysteine desulfurase, IscS, has a major role in in vivo Fe-S cluster formation in Escherichia coli. 1090 75

The proton-pumping NADH:ubiquinone oxidoreductase, also called complex I, is the first of the respiratory complexes providing the proton motive force which is essential for energy consuming processes like the synthesis of ATP. Homologues of this complex exist in bacteria, archaea, in mitochondria of eukaryotes and in chloroplasts of plants. The bacterial and mitochondrial complexes function as NADH dehydrogenase, while the archaeal complex works as F420H2 dehydrogenase. The electron donor of the cyanobacterial and plastidal complex is not yet known. Despite the different electron input sites, 11 polypeptides constitute the structural framework for proton translocation and quinone binding in the complex of all three domains of life. Six of them are also present in a family of membrane-bound multisubunit [NiFe] hydrogenases. It is discussed that they build a module for electron transfer coupled to proton translocation.
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PMID:The respiratory complex I of bacteria, archaea and eukarya and its module common with membrane-bound multisubunit hydrogenases. 1094 Mar 77

The membrane-bound NADH dehydrogenase of an alkaliphilic Bacillus YN-1 involved in the respiratory chain exhibits reductase activity for hydrogen peroxide and cumene hydroperoxide in the presence of the 22-kDa component (AhpC) from Amphibacillus xylanus (Koyama et al. Biochem. Biophys. Res. Commun. 247, 659-662). In this study, AhpC-like polypeptide with an apparent molecular mass of 20 kDa was isolated from the cell-free extract of YN-1. The NADH dehydrogenase exhibited reductase activity for cumene hydroperoxide in the presence of the purified AhpC-like component from YN-1. It is likely that the NADH dehydrogenase is not only involved in the respiratory chain, but also functions for scavenging peroxide in the presence of its own endogenous AhpC component. The enzyme expressed in Escherichia coli as a fusion protein with glutathione S-transferase (GST) showed the NADH dehydrogenase activity as high as the native enzyme from YN-1. While the fusion protein was unable to reduce cumene hydroperoxide in the presence of AhpC-like protein from YN-1, the protein obtained by the cleavage treatment of the fusion protein to release GST exhibited the reductase activity as much as the native enzyme.
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PMID:Peroxide reductase activity of NADH dehydrogenase in the presence of an endogenous 20-kDa component of an alkaliphilic Bacillus. 1108 Mar 86

Purpose: To clarify the function of ascorbate free radical (AFR) reductase in the lens antioxidation mechanism, we investigated the difference among species in AFR reductase activity in different vertebrate lenses.Materials and Methods: Soluble and insoluble fractions were prepared from the lenses of frogs, guinea pigs, rats, rabbits, pigs, and calves. AFR reductase and diaphorase activity of each fraction was determined.Results: AFR reductase activity in the lens soluble fraction was the highest in frogs. That of guinea pigs and rabbits was at the next level; there was only a little activity in rats and pigs, and none was detected in calves. Membrane-bound AFR reductase in the lens insoluble fraction was extracted by 0.3% Triton X-100. The membrane-bound enzyme activity was almost at the same level in frogs, rats, rabbits, and calves, and a little higher in guinea pigs and pigs. However, such species-specificity of AFR reductase activity as in the soluble fraction was not observed in 0.3% Triton X-100 extracts. Diaphorase activity was 3 to 9 times as much as AFR reductase activity in the soluble fractions of frogs, guinea pigs, and rabbits, but in 0.3% Triton X-100 extracts of all vertebrate species used, it was very high, 108 to 311 times the AFR reductase activity.Conclusion: These results suggest that the lens soluble and membrane-bound AFR reductases are individual enzyme molecules and have different anti-oxidative functions. The lenses of frogs, guinea pigs, and rabbits contain a near-ultraviolet (UV) light absorbing compound, reduced pyridine nucleotide at a high concentration. Therefore, the soluble AFR reductase activity may be high in the vertebrate lenses with a near-UV light filter, and enhance the antiphotoxidation of ascorbic acid.
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PMID:Ascorbate Free Radical Reductase Activity in Vertebrate Lenses of Some Species. 1109 3

Hypoxic pulmonary vasoconstriction (HPV) is a regulatory feature of the pulmonary circulation that ensures consistent matching of perfusion to ventilation in the normal lung. However, under pathophysiological conditions, HPV contributes to the elevated pulmonary arterial pressure inherent to numerous disease states. Consequently, control of HPV is an avenue of potential therapy for such conditions. This review discusses the role of hydrogen peroxide (H(2)O(2)) as an intracellular signal in the pulmonary circulation, concentrating on the potential involvement of H(2)O(2) in HPV and in the control of pulmonary arterial tone. Sites of hypoxic pulmonary arterial H(2)O(2) production include the mitochondrial electron transport chain, a microsomal electron transport chain containing an NADH oxidoreductase and alternatively, a membrane-bound NADPH oxidase. Each of these sources of H(2)O(2) and the effect of hypoxia on the production of reactive oxygen species are considered. The review also discusses the variance in vascular reactivity of H(2)O(2), which is described to elicit both pulmonary arterial vasoconstriction and dilatation at varying concentrations. The redox capabilities of H(2)O(2) are also considered. The relevance of all of these actions of H(2)O(2) are also assessed as potential pharmacological targets for the future development of therapy for lung diseases that are characterised by some degree of HPV and in the pathogenesis of pulmonary diseases in which reactive oxygen species are implicated.
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PMID:Hydrogen peroxide--an intracellular signal in the pulmonary circulation: involvement in hypoxic pulmonary vasoconstriction. 1115 May 95

From phylogenetic sequence analysis, it can be concluded that the proton-pumping NADH:ubiquinone oxidoreductase (complex I) has evolved from preexisting modules for electron transfer and proton translocation. It is built up by a peripheral NADH dehydrogenase module, an amphipatic hydrogenase module, and a membrane-bound transporter module. These modules, or at least part of them, are also present in various other bacterial enzymes. It is assumed that they fulfill a similar function in complex I and related enzymes. Based on the function of the individual modules, it is possible to speculate about the mechanism of complex I. The hydrogenase module might work as a redox-driven proton pump, while the transporter module might act as a conformation-driven proton pump. This implies that complex I contains two energy-coupling sites. The NADH dehydrogenase module seems to be involved in electron transfer and not in proton translocation.
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PMID:Complex I: a chimaera of a redox and conformation-driven proton pump? 1169 26

In the O2- generating flavocytochrome b, the membrane-bound component of the neutrophil NADPH oxidase, electrons are transported from NADPH to O2 in the following sequence: NADPH --> FAD --> heme b -->O2. Although p-iodonitrotetrazolium (INT) has frequently been used as a probe of the diaphorase activity of the neutrophil flavocytochrome b, the propensity of its radical to interact reversibly with O2 led us to question its specificity. This study was undertaken to reexamine the interaction of INT with the redox components of the neutrophil flavocytochrome b. Two series of inhibitors were used, namely the flavin analog 5-deaza FAD and the heme inhibitors bipyridyl and benzylimidazole. The following results indicate that INT reacts preferentially with the hemes rather than with the FAD redox center of flavocytochrome b and is not therefore a specific probe of the diaphorase activity of flavocytochrome b. First, in anaerobiosis, reduced heme b in activated membranes was reoxidized by INT as efficiently as by O2 even in the presence of concentrations of 5-deaza FAD which fully inhibited the NADPH oxidase activity. Second, the titration curve of dithionite-reduced heme b in neutrophil membranes obtained by oxidation with increasing amounts of INT was strictly superimposable on that of dithionite-reduced hemin. Third, INT competitively inhibited the O2 uptake by the activated NADPH oxidase in a cell-free system. Finally, the heme inhibitor bipyridyl competitively inhibited the reduction of INT in anaerobiosis, and the oxygen uptake in aerobiosis.
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PMID:Exploration of the diaphorase activity of neutrophil NADPH oxidase. 1185 58

NADH dehydrogenase-2 (NDH-2) from Escherichia coli is a membrane-bound flavoprotein linked to the respiratory chain. We have previously shown that this enzyme has cupric reductase activity that is involved in hydroperoxide-induced oxidative stress. In this paper we present spectroscopic evidence that NDH-2 contains thiolate-bound Cu(I) with luminescence properties. Purified NDH-2 exhibits an emission band at 670nm with excitation wavelengths of 280 and 580nm. This emission is quenched by the specific Cu(I) chelator bathocuproine disulfonate, but not by EDTA. The luminescence intensity is sensitive to the enzyme substrates and, thus, the Cu(I)-thiolate chromophore reflects the redox and/or conformational states of the protein. There is one copper atom per polypeptide chain of the purified NDH-2, as determined by atomic absorption spectroscopy. Bioinformatics allowed us to recognize a putative copper-binding site and to predict four structural/functional domains in NDH-2: (I) the FAD-binding domain, (II) the NAD(H)-binding domain, (III) the copper-binding domain, and (IV) the domain of anchorage to the membrane containing two transmembrane helices, at the C-terminus. A NDH-2 topology model, based on the secondary structure prediction, is proposed. This is the first description of a copper-containing NADH dehydrogenase. Comparative sequence analysis allowed us to identify a branch of homologous dehydrogenases that bear a similar metal-binding motif.
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PMID:Evidence for Cu(I)-thiolate ligation and prediction of a putative copper-binding site in the Escherichia coli NADH dehydrogenase-2. 1217 61

Defects of the NADH dehydrogenase complex are predominantly manifested in mitochondrial diseases and are significantly associated with the development of many late onset neurological disorders such as Parkinson's disease. Here we describe an immunocapture procedure for isolating this multisubunit membrane-bound complex from human tissue. Using small amounts of immunoisolated protein, one-dimensional and two-dimensional gel electrophoresis, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) peptide mass finger printing (PMF), and nanoflow liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS), we can resolve and identify the human homologues of 42 polypeptides detected so far in the more extensively studied beef heart complex I. These polypeptides include the GRIM-19 protein, which is claimed to be involved in apoptosis, a polypeptide first identified by gene screening as a neuronal protein, as well as a protein thought to be in differentiation linked processes. The concordance of data from human and bovine complex I isolated by different procedures adds to the certainty that these novel proteins of seemingly diverse function are a part of complex I.
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PMID:The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification. 1261 91

Complex III of the mitochondrial electron transport chain, ubiquinol-cytochrome c reductase, was isolated by blue native polyacrylamide gel electrophoresis. Ten of the 11 polypeptides present in this complex were detected directly by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) following electroelution of the active complex. Tryptic and chymotryptic digestion of the complex permit the identification of specific peptides from all of the protein subunits with 70% coverage of the 250 kDa complex. The mass of all 11 proteins was confirmed by second dimension Tricine sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and elution of the separated polypeptides. Additionally, the identity of the core I, core II, cytochrome c and the Rieske iron-sulfur protein were confirmed by liquid chromatography/tandem mass spectrometry (LC/MS/MS) characterization of the peptides generated by in-gel trypsin digestion of the SDS-PAGE separated proteins. The methodology demonstrated for analyzing this membrane-bound electron transport complex should be applicable to other membrane complexes, particularly the other mitochondrial electron transport complexes. The MS analysis of the peptides obtained by in-gel digestion of the intact complex permits the simultaneous characterization of the native proteins and modifications that contribute to mitochondrial deficits that have been implicated as contributing to pathological conditions.
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PMID:Mass spectrometric characterization of mitochondrial electron transport complexes: subunits of the rat heart ubiquinol-cytochrome c reductase. 1279 75


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