Disease relevance of gor

• Furthermore, in anaerobiosis, E. coli is dependent for growth on class III RNR, NrdDG, and on having at least one of the two reductive systems, thioredoxin reductase or glutathione reductase [1].
• Molecular characterization of the gor gene encoding glutathione reductase from Pseudomonas aeruginosa: determinants of substrate specificity among pyridine nucleotide-disulphide oxidoreductases [2].
• The glutathione reductase gene, gor, was cloned from the plant pathogen Xanthomonas campestris pv. phaseoli [3].
• Characterization of the gor gene of the lactic acid bacterium Streptococcus thermophilus CNRZ368 [4].
• Interestingly, its expression and enzyme characteristics were different from GR homologue of filarial parasite O. volvulus [5].

High impact information on gor

• It led to a mutant form of E. coli glutathione reductase that possessed essentially no activity with glutathione but that was able to catalyze trypanothione reduction with a kcat/Km value that was 10% of that measured for natural trypanothione reductases [6].
• Thioredoxin reductase contains a redox active disulfide and is a member of the pyridine nucleotide-disulfide oxidoreductase family of flavoenzymes that includes lipoamide dehydrogenase, glutathione reductase, trypanothione reductase, mercuric reductase, and NADH peroxidase [7].
• Modeling of NADP+ in the active site revealed that LpdA achieves the high specificity for NADP+ through interactions involving the 2'-phosphate of NADP+ and amino acid residues that are different from those in glutathione reductase [8].
• Experiments with the phototrophic alpha proteobacterium Rhodospirillum rubrum showed that the rate of selenite reduction was decreased when bacteria synthesized lower than normal levels of glutathione, and in Rhodobacter sphaeroides and Escherichia coli the reaction was reported to induce glutathione reductase [9].
• Regeneration of ascorbate is achieved by monodehydroascorbate reductase (EC 1.6.5.4) using NAD(P)H as an electron donor or, alternatively, by a set of two coupled reactions requiring dehydroascorbate reductase, glutathione reductase, glutathione, and NAD(P)H [10].

Chemical compound and disease context of gor

• The cloned Escherichia coli gor gene encoding the flavoprotein glutathione reductase was placed under the control of the tac promoter in the plasmid pKK223-3, allowing expression of glutathione reductase at levels approximately 40,000 times those of untransformed cells [11].
• An expression vector, pKGR, for the gor gene from Escherichia coli encoding glutathione reductase was constructed by subcloning of an AvaII fragment of the Clarke & Carbon bank plasmid pGR [Greer & Perham (1986) Biochemistry 25, 2736-2742] into the plasmid pKK223-3 [12].
• The gene gor encoding Escherichia coli glutathione reductase was mutated to create a positively charged N-terminal extension consisting of five arginine residues followed by a factor Xa cleavage site to the enzyme polypeptide chain [13].
• Data on glutathione status and cystine reduction in the E. coli gsh and gor mutants suggested that exogenous cystine at first should be reduced with extracellular GSH outside the cells and then imported into them [14].
• Glutathione reductase from Escherichia coli is inactivated when incubated with either NADPH or NADH [15].

Biological context of gor

• The P. aeruginosa gor gene was identified by hybridization with a short DNA sequence from the gene encoding mercuric reductase in transposon Tn501 [2].
• By directed mutagenesis of the gor gene, His-439 was changed to glutamine (H439Q) and alanine (H439A) [11].
• A gor knockout mutant was constructed and shown to have increased expression of the organic peroxide-inducible regulator gene, ohrR [3].
• The gor gene maps between min 77 and 78 on the E. coli genome, and the mutation causes no growth defect [16].
• The unique glutathione reductase from Xanthomonas campestris: gene expression and enzyme characterization [3].

Anatomical context of gor

• Subgenes encoding three forms of the interface domain have been expressed in E. coli and the products purified from inclusion bodies: INT is the excised interface domain, as it is found in native GR; INTN and INTFN are variants carrying exchanges of surface residues in what would have been hydrophobic contact regions with other neighboring domains [17].
• Additionally, a sequence comparison of the glutathione reductase from Escherichia coli or human erythrocytes to T. congolense trypanothione reductase reveals greater than 50% homology [18].
• Ascorbic acid deficiency did not influence the activities of glutathione reductase and myeloperoxidase of leukocytes [19].
• In this system we found that co-expression of glutathione reductase remarkably increased accumulation level of 20K hGH in periplasm and confirmed that secreted 20K hGH was correctly processed [20].
• At constant substrate concentrations the potential would depend primarily on activity of the cytosol glutathione reductase (NAD(P)H: oxidized-glutathione oxidoreductase, EC 1.6.4.2) relative to that of the membrane-bound monooxygenase [21].

Associations of gor with chemical compounds

• However, unlike the schistosome Prxs, FhePrx could not utilise reducing equivalents supplied by glutathione or glutathione reductase [22].
• The path of reducing equivalents in catalysis by glutathione reductase and lipoamide dehydrogenase is clear [7].
• Structure of the NADPH-binding motif of glutathione reductase: efficiency determined by evolution [23].
• Trypanothione reductase of Trypanosoma congolense: gene isolation, primary sequence determination, and comparison to glutathione reductase [18].
• In most of the mutant enzymes, the Km for NADPH was substantially greater than that found for wild-type glutathione reductase, as expected, but this was accompanied by an unexpected decrease in the Km for GSSG [23].

Analytical, diagnostic and therapeutic context of gor

• Sequence analysis of the gene indicated that it is most likely derived from a Pseud monas sp. The gene is located immediately upstream and transcribed in the same direction of the gor (glutathione reductase) gene and is capable of encoding a protein 30,943 daltons in size [24].
• The role of the second glycine residue (Gly-176) of the conserved GXGXXA "fingerprint" motif in the NADPH-binding domain of Escherichia coli glutathione reductase has been studied by means of site-directed mutagenesis [23].
• A designed mutant of the enzyme glutathione reductase shortens the crystallization time by a factor of forty [25].
• Reduction of disulfide bonds between the alpha- and beta-tubulin subunits by the glutathione reductase system was assessed by Western blot [26].
• Northern blot analysis and glutathione reductase enzyme assays gave evidence that the gene is expressed in aerobically growing cells [4].

References