Disulfide oxidoreductases

Bartley, G.E. et al.. Carotenoid desaturases from Rhodobacter capsulatus and Neu-rospora crassa are structurally and functionally conserved and contain domains homologous to flavoprotein disulfide oxidoreductases, J. Biol. Chem. 265, 16020, 1990. 

Xanthobacter sp. strain Py2 may be grown with propene or propene oxide. On the basis of amino acid sequences, the monooxygenase that produces the epoxide was related to those that catalyzes the monooxygenation of benzene and toluene (Zhou et al. 1999). The metabolism of the epoxide is initiated by nucleophilic reaction with coenzyme M followed by dehydrogenation (Eigure 7.13a). There are alternative reactions, both of which are dependent on a pyridine nucleotide-disulfide oxidoreductase (Swaving et al. 1996 Nocek et al. 2002) ... 

Nocek B, SB Jang, MS Jeong, DD Clark, SA Ensign, JW Peters (2002) Structural basis for COj fixation by a novel member of the disulfide oxidoreductase family of enzymes, 2-ketopropyl-coenzyme M oxidore-ductase/carboxylase. Biochemistry Al 12907-12913. 

Mammalian thioredoxin reductases are a family of selenium-containing pyridine nucleotide-disulfide oxidoreductases. These enzymes catalyze NADPH-dependent reduction of the redox protein thioredoxin (Trx), which contains a redox-active disulfide and dithiol group and by itself may function as an efficient cytosolic antioxidant [77]. One of the functions of Trx/ thioredoxin reductase system is the NADPH-catalyzed reduction of protein disulfide [78] ... 

Bouwman, C. W., Kohli, M., Killoran, A., Touchie, G. A., Kadner, R. J., and Martin, N. F. (2003). Characterization of SrgA, a Salmonella enterica serovar Tjrphimurium virulence plasmid-encoded paralogue of the disulfide oxidoreductase DsbA, essential for biogenesis of plasmid-encoded fimbriae. /. Bacteriol. 185, 991-1000. 

Aslund, E, Bemdt, K.D., Holmgren, A. Redox potentials of glutaredoxins and other thiol-disulfide oxidoreductases of the thioredoxin superfamily determined by direct protein-protein redox equilibria. J Biol Chem 272(49), 30780-30786 (1997)... 

Pyridine nucleotide-dependent flavoenzyme catalyzed reactions are known for the external monooxygenase and the disulfide oxidoreductases However, no evidence for the direct participation of the flavin semiquinone as an intermediate in catalysis has been found in these systems. In contrast, flavin semiquinones are necessary intermediates in those pyridine nucleotide-dependent enzymes in which electron transfer from the flavin involves an obligate 1-electron acceptor such as a heme or an iron-sulfur center. Examples of such enzymes include NADPH-cytochrome P4S0 reductase, NADH-cytochrome bs reductase, ferredoxin — NADP reductase, adrenodoxin reductase as well as more complex enzymes such as the mitochondrial NADH dehydrogenase and xanthine dehydrogenase. 

Both thioredoxin and glutaredoxin are members of a larger group of thiol disulfide oxidoreductases which are found in all known organisms. In E. coli there are one thioredoxin, three different glutaredoxins,h/t and the periplasmic protein disulfide... 

Both MAO-A and MAO-B contain a redox-active disulfide at the catalytic center. The results imply that MAO may be a novel type of disulfide oxidoreductase and may open the way to characterizing the catalytic and chemical mechanism of the enzyme. 

When an amine is oxidized, electrons pass from the amine to the disulfide and then to the flavin. The formation in MAO of a carboxyl-imidazole-disulfide triad, similar to that demonstrated for disulfide oxidoreductases, would result in an increased positive charge on the disulfide,... 

Figure 12.18. Output of Pfam search results. Pfam search is performed with amino acid sequence derived from lipoamide dehydrogenase (Schizosaccharomyces pombe). The table for the trusted matches from Pfam-A for pyr redox (pyridine nucleotide disulfide oxidoreductase) and pyr redox dim (pyridine nucleotide disulfide oxidoreductase, dimerization) domains and their alignments (partial) to HMMs ( ->) are shown. The trusted matches from Pfam-B, the potential matches (Thi4 for thiamine biosynthetic enzyme domain), and the bead-on-a-string sketches are not shown. Select the linked domain name to view the functional description of the domain. The HMM alignments are followed by an option button (Align to seed or Align to family) that enables the user to view/save the multiple alignment of each matched family.

TrxRs are homodimeric flavoproteins [80] that catalyze the NADPH-dependent reduction of thioredoxin (Trx), a ubiquitous 12 kDa protein that is the major protein disulfide reductase in cells [81], and belongs to the pyridine nucleotide-disulfide oxidoreductase family [82]. Each monomer includes an FAD prosthetic group, a NADPH binding site and an active site containing a redox-active selenol group. Electrons are transferred from NADPH via FAD to the active-site selenol of TrxR, which then reduces the substrate Trx [83]. The crystal structure of TrxR is shown in Fig. 13 [84],... 

The pyridine nucleotide-disulfide oxidoreductases, lipoamide dehydrogenase (4), glutathione reductase (5), and thioredoxin reductase (6-8) share so many properties in common that they will be compared and contrasted before being considered separately. As their group name implies, they catalyze the transfer of electrons between pyridine nucleotides and disulfides. In spite of their similarities they function in widely divergent metabolic roles. 

The gross structure of the pyridine nucleotide-disulfide oxidoreductases is the same, i.e., two polypeptide chains each containing a redox active... 

Amino Acid Analysis of Pyridine Nucleotide-Disulfide Oxidoreductases"... 

The specificity of glutathione reductase toward its disulfide substrate was emphasized in Section II,A, since there is virtually no reactivity with the substrates of the other pyridine nucleotide-disulfide oxidoreductases. Other authors have emphasized the lack of specificity of this enzyme since it can catalyze the reduction of a variety of mixed disulfides provided that glutathione or y-glutamylcysteine comprises one-half (IP5, 21%) Table IV summarizes these (39, 226-231). It is important to distin-... 

Lecithin, transhydrogenase and, 70-71 Leucine residues disulfide oxidoreductases, 104 glyceraldehyde-3-phosphate dehydrogenase, 11, 12... 

NADH peroxidase (Npx EC 1.11.1.1) and NADH oxidase (Nox EC 1.6.99.x) are disulfide oxidoreductases-related enzymes that contain a single redox-active cysteine (16). They supply strictly fermentative bacteria with NAD+ for glycolysis and play an important role in redox signaling in response to oxidative and nitrosative stress (19). 

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