Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.37 (malate dehydrogenase)
 4,591 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The reactivity of human thioredoxin (HTR) was tested in several reactions. HTR was as efficient as E. coli or plant and algal thioredoxins when assayed with E. coli ribonucleotide reductase or for the reduction of insulin. On the other hand, HTR was poorly reduced by NADPH and the E. coli flavoenzyme NADPH thioredoxin reductase as monitored in the DTNB reduction test. When reduced with dithiothreitol (DTT), HTR was much less efficient than thioredoxin m and thioredoxin f, the respective specific thioredoxins for the chloroplast enzymes NADP-malate dehydrogenase (NADP-MDH) and fructose 1,6 bisphosphatase (FBPase). Finally, HTR could be used in the photoactivation of NADP-MDH although less efficiently than thioredoxin m, proving nevertheless that it can be reduced by the iron sulfur enzyme ferredoxin thioredoxin reductase in the presence of photoreduced ferredoxin. Based on sequence comparisons, it was expected that HTR would display a reactivity similar to chloroplast thioredoxin f rather than to thioredoxin m. However the observed behavior of FTR did not exactly fit this prediction. The results are discussed in relation to the structural data available for the proteins.
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PMID:Human thioredoxin reactivity-structure/function relationship. 217 90

Thioredoxins have been purified from pig heart and potato tuber mitochondria which differ in chromatographic behaviour, enzyme activating capacity, and slightly higher molecular mass (Mr = 12,500) from the major thioredoxin(s) present in mitochondria-free fractions of the same tissue. Both mt-thioredoxins can serve as hydrogen donor for E. coli ribonucleotide reductase but only the plant protein activates spinach chloroplast NADP malate dehydrogenase in vitro. Mitochondrial target enzymes specifically activated by thioredoxin have not as yet been identified.
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PMID:Animal and plant mitochondria contain specific thioredoxins. 259 33

A second thioredoxin, distinct from the one reported by Meng and Hogenkamp in 1981 (J. Biol. Chem. 256, 9174-9182), has been purified to homogeneity from an Escherichia coli strain containing a plasmid encoding a Corynebacterium nephridii thioredoxin. Thioredoxin genes from C. nephridii were cloned into the plasmid pUC13 and transformants were identified by complementation of a thioredoxin negative (trxA-) E. coli strain. The abilities of the transformants to support the growth of several phages suggested that more than one thioredoxin had been expressed [Lim et al. (1987) J. Biol. Chem. 262, 12114-12119]. In this paper we present the purification and characterization of one of these thioredoxins. The new thioredoxin from C. nephridii, designated thioredoxin C-2, is a heat-stable protein containing three cysteine residues/molecule. It serves as a substrate for C. nephridii thioredoxin reductase and E. coli and Lactobacillus leichmannii ribonucleotide reductases. Thioredoxin C-2 catalyzes the reduction of insulin disulfides by dithiothreitol or by NADPH and thioredoxin reductase and is a hydrogen donor for the methionine sulfoxide reductase of E. coli. Spinach malate dehydrogenase (NADP+) and phosphoribulokinase are activated by this thioredoxin while glyceraldehyde-3-phosphate dehydrogenase (NADP+) is not. Like the thioredoxin first isolated from C. nephridii, this new thioredoxin is not a reducing substrate for the C. nephridii ribonucleotide reductase. The complete primary sequence of this second thioredoxin has been determined. The amino acid sequence shows a high degree of similarity with other thioredoxins. Surprisingly, in contrast to the other sequences, this new thioredoxin contains the tetrapeptide -Cys-Ala-Pro-Cys- at the active site. With the exception of the T4 thioredoxin, this is the first example of a thioredoxin that does not have the sequence -Cys-Gly-Pro-Cys-. Our results suggest that, like plant cells, bacterial cells may utilize more than one thioredoxin.
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PMID:Purification, characterization and revised amino acid sequence of a second thioredoxin from Corynebacterium nephridii. 291 72

Two thioredoxin fractions had previously been reported to occur in Anabaena 7119 by Buchanan and co-workers (Yee, B. C., dela Torre, A., Crawford, N. A., Lara, C., Carlson, D. E., and Buchanan, B. B. (1981) Arch. Microbiol. 130, 14-18). These proteins were detected by their ability to activate spinach fructose-1,6-bisphosphatase (Fru-P2-ase). The partially purified proteins resembled similar thioredoxins found in spinach chloroplasts and were designated thioredoxin f (Tf) for the fraction most effective in activating spinach Fru-P2-ase and thioredoxin m (Tm) for the fraction most effective in activating spinach NADPH-malate dehydrogenase. Using the assay system of Yee and co-workers, we were able to separate and purify to homogeneity two thioredoxin fractions from Anabaena extracts. Tm corresponded to the thioredoxin fraction we had isolated and studied previously (Gleason, F. K., and Holmgren, A. (1981) J. Biol. Chem. 256, 8301-8309). The other fraction, Tf, was characterized further. Unlike the thioredoxins found in higher plants, the cyanobacterial thioredoxins do not appear to be related. Anabaena thioredoxin f has a Mr = 25,500 as compared to the more usual Mr = 12,000 for Tm. From a comparison of the amino acid composition, Tf is not obviously a dimer or otherwise related to Tm. Tf has one active center cystine disulfide. Anabaena Tf activates spinach Fru-P2-ase very efficiently but has very little activity with spinach malate dehydrogenase. Anabaena Tf, unlike Tm, does not reduce the homologous ribonucleotide reductase. Anabaena Tf also does not activate a partially purified preparation of Anabaena Fru-P2-ase. We conclude that the cyanobacterial Tf is a unique protein with no structural or functional properties in common with other thioredoxins.
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PMID:Isolation and characterization of thioredoxin f from the filamentous cyanobacterium, Anabaena sp. 7119. 609 40

A thioredoxin has been highly purified from rabbit bone marrow. This thioredoxin is heat-stable, has a molecular weight of approximately 13,000, and contains 4 half-cystines. It is a substrate for the NADPH-dependent thioredoxin reductase of rabbit bone marrow, catalyzes the reduction of insulin disulfides by dithiothreitol, and is a hydrogen donor for methionine sulfoxide reductase of yeast. Although active as a hydrogen donor for ribonucleotide reductase of Lactobacillus leichmannii, this activity could not be demonstrated when the bone marrow thioredoxin was tested with the ribonucleotide reductases of rabbit bone marrow and Corynebacterium nephridii. A regulatory role for the bone marrow thioredoxin was investigated by determining its ability to activate two of the enzymes of spinach chloroplasts known to require thioredoxin for their activation. The bone marrow thioredoxin effectively activates spinach NADP-malate dehydrogenase but not spinach fructose 1,6-diphosphatase. These observations suggest that instead of serving as a hydrogen donor for ribonucleotide reduction in bone marrow, this thioredoxin may be involved in the regulation of the activity of bone marrow enzyme(s).
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PMID:Properties of a thioredoxin purified from rabbit bone marrow which fails to serve as a hydrogen donor for the homologous ribonucleotide reductase. 635 4

Thioredoxin systems composed of several thioredoxin isoproteins and a NADPH: thioredoxin reductase are contained in the albumin-globulin fraction of wheat and soy-bean seed proteins. Two wheat thioredoxins I and II were separated on CM-cellulose whereas soy-bean extracts could be resolved into three thioredoxins I, II, and III on DEAE-cellulose. These proteins were purified to apparent homogeneity and were shown by sodium dodecylsulfate/polyacrylamide gel electrophoresis to possess the molecular weight Mr identical to 12000 typical of the single bacterial and animal thioredoxin. In contrast, gel filtration runs may yield erroneous estimates of thioredoxin molecular weights. The seed thioredoxins can serve as ribonucleotide reductase (Escherichia coli) substrates. They stimulate spinach NADP: malate dehydrogenase but are inactive towards chloroplast fructose-bisphosphatase. These results demonstrate that the number of thioredoxins in nongreen plant tissues approaches that of leaves; additional explanations must therefore be sought for the multiple thioredoxin profiles of plants besides diversification for light-dependent and light-independent functions.
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PMID:Plant seeds contain several thioredoxins of regular size. 668 37

Infections with the microaerophilic parasite Trichomonas vaginalis are treated with the 5-nitroimidazole drug metronidazole, which is also in use against Entamoeba histolytica, Giardia intestinalis and microaerophilic/anaerobic bacteria. Here we report that in T. vaginalis the flavin enzyme thioredoxin reductase displays nitroreductase activity with nitroimidazoles, including metronidazole, and with the nitrofuran drug furazolidone. Reactive metabolites of metronidazole and other nitroimidazoles form covalent adducts with several proteins that are known or assumed to be associated with thioredoxin-mediated redox regulation, including thioredoxin reductase itself, ribonucleotide reductase, thioredoxin peroxidase and cytosolic malate dehydrogenase. Disulphide reducing activity of thioredoxin reductase was greatly diminished in extracts of metronidazole-treated cells and intracellular non-protein thiol levels were sharply decreased. We generated a highly metronidazole-resistant cell line that displayed only minimal thioredoxin reductase activity, not due to diminished expression of the enzyme but due to the lack of its FAD cofactor. Reduction of free flavins, readily observed in metronidazole-susceptible cells, was also absent in the resistant cells. On the other hand, iron-depleted T. vaginalis cells, expressing only minimal amounts of PFOR and hydrogenosomal malate dehydrogenase, remained fully susceptible to metronidazole. Thus, taken together, our data suggest a flavin-based mechanism of metronidazole activation and thereby challenge the current model of hydrogenosomal activation of nitroimidazole drugs.
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PMID:Trichomonas vaginalis: metronidazole and other nitroimidazole drugs are reduced by the flavin enzyme thioredoxin reductase and disrupt the cellular redox system. Implications for nitroimidazole toxicity and resistance. 1941 1