Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nine cysteines are found in the deduced amino acid sequences of both human liver monoamine oxidase (MAO)-A and MAO-B. The role of these cysteine residues in MAO-A and -B catalytic activity was studied by site-directed mutagenesis, whereby each cysteine residue was converted to serine. The wild-type and mutant cDNAs were then transiently transfected into COS cells and assayed for MAO-A and -B catalytic activity using 5-[3H]hydroxytryptamine and [14C]phenylethylamine, respectively, as substrates. Catalytic activities were retained in seven MAO-A cysteine to serine mutants (mutations at residues 165, 210, 266, 306, 321, 323, and 398) and in six MAO-B cysteine to serine mutants (mutations at residues 5, 172, 192, 297, 312, and 389). Kinetic parameters (Km) of these mutants were also similar to those of the wild-type enzymes, indicating that these cysteines are not necessary for enzymatic activity. Substitution of MAO-A Cys-374 and -406 and MAO-B Cys-156, -365, and -397 with serine resulted in complete loss of MAO-A and -B catalytic activity. The loss of catalytic activity was not due to unsuccessful transfection of the mutants, as indicated by either Northern blot or Western blot analysis. The loss of catalytic activity in the MAO-A Ser-406 and MAO-B Ser-397 mutants may be due to the prevention of covalent binding of the enzyme to the cofactor FAD, which is necessary for catalytic activity. The loss of catalytic activity of MAO-A Ser-374 and MAO-B Ser-156 and -365 suggests that these cysteines are important for catalytic activity, but whether they are involved in forming the active site or are important for the appropriate conformation of MAO-A and -B remains to be studied.
Mol Pharmacol 1993 Jun
PMID:Site-directed mutagenesis of monoamine oxidase A and B: role of cysteines. 831 21

Superoxide is produced by phagocytic cells at rates sufficient to have cytocidal effects. A wide variety of receptor-dependent and -independent agonists triggers this respiratory burst, including immunoglobin aggregates, complement fragments, and leukotriene B4. Lower rates of O2-. production are triggered by addition of specific cytokines into B-lymphocytes, endothelial cells, fibroblasts, and kidney mesangial cells; low concentration of radicals may act as signals for proliferation or other changes. The NADPH oxidase of phagocytes, characterized by the presence of FAD and a low potential cytochrome b, is organized to transfer electrons electrogenically across the plasma membrane from NADPH to O2. A proton channel permits movement of compensating H+.
Mol Chem Neuropathol
PMID:The mechanism of the production of superoxide by phagocytes. 839 50

The activity of FAD-glycerophosphate dehydrogenase, as measured through the generation of either 3HOH from L-[2-3H]glycerol-3-phosphate in the presence of FAD or iodoformazan from iodonitrotetrazolium, displayed comparable values in islet homogenates of lean and obese (ob/ob) mice. In the liver of the obese animals, the results obtained by the colorimetric and radioisotopic assays yielded a paired ratio twice higher than in control mice. Although isoforms of the mitochondrial enzyme could be present in variable proportions depending on the cell type and genetic background, the present results suggest that, in ob/ob mice, the increased secretory responsiveness of the islet B-cell to D-glucose coincides with an unaltered activity of FAD-glycerophosphate dehydrogenase. This contrasts with the situation recently documented in db/db mice, in which an impaired secretory response of the B-cell to D-glucose is associated with a decreased activity of FAD-glycerophosphate dehydrogenase.
Biochem Mol Biol Int 1993 Jul
PMID:FAD-glycerophosphate dehydrogenase activity in pancreatic islets and liver of ob/ob mice. 840 Dec 96

Glucose oxidase (beta-D-glucose: oxygen 1-oxidoreductase, EC 1.1.3.4) is an FAD-dependent enzyme that catalyzes the oxidation of beta-D-glucose by molecular oxygen. The crystal structure of the partially deglycosylated enzyme from Aspergillus niger has been determined by isomorphous replacement and refined to 2.3 A resolution. The final crystallographic R-value is 18.1% for reflections between 10.0 and 2.3 A resolution. The refined model includes 580 amino acid residues, the FAD cofactor, six N-acetylglucosamine residues, three mannose residues and 152 solvent molecules. The FAD-binding domain is topologically very similar to other FAD-binding proteins. The substrate-binding domain is formed from non-continuous segments of sequence and is characterized by a deep pocket. One side of this pocket is formed by a six-stranded antiparallel beta-sheet with the flavin ring system of FAD located at the bottom of the pocket on the opposite side. Part of the entrance to the active site pocket is at the interface to the second subunit of the dimeric enzyme and is formed by a 20-residue lid, which in addition covers parts of the FAD-binding site. The carbohydrate moiety attached to Asn89 at the tip of this lid forms a link between the subunits of the dimer.
J Mol Biol 1993 Jan 05
PMID:Crystal structure of glucose oxidase from Aspergillus niger refined at 2.3 A resolution. 842 Dec 98

The structure of the complex between cofactor NADH and the enzyme NADH peroxidase from Streptococcus faecalis 10C1 (Enterococcus faecalis) has been determined by crystal soaking, X-ray data collection, model building of NADH and refinement at 0.24-nm resolution based on the known enzyme structure [Stehle, T., Ahmed, S. A., Claiborne, A. & Schulz, G. E. (1991) J. Mol. Biol. 221, 1325-1344]. Apart from NADH, the catalytic center of the enzyme contains FAD and a cysteine that shuttles between thiolate and sulfenic acid states. Unfortunately, this cysteine was irreversibly oxidized to a cysteine sulfonic acid in the established enzyme structure. Based on the geometry of the catalytic center, we discuss the stabilization of the oxidation-sensitive sulfenic acid and propose a reaction mechanism.
 ...
PMID:NADH binding site and catalysis of NADH peroxidase. 842 32

Previously, we provided evidence that cysteine conjugate S-oxidase (S-oxidase) activities of rat liver and kidney microsomes may be associated with flavin-containing monooxygenases (FMOs). In this study, the biochemical properties of these activities were further investigated. When NADPH was replaced by NADH, the S-oxidase activities were reduced significantly. Removal of the flavin moiety from microsomes significantly reduced the S-oxidase activities; however, addition of exogenous FAD or FMN restored the activities of the flavin-depleted microsomes. Solubilization of hepatic or renal microsomes with Emulgen 911, Nonidet P-40, Triton X-100, or 3-[(3-cholamidopropyl)dimethyl-ammonio]-1- propane sulfate or inclusion of the sulfhydryl-reactive agents Hg2+, N-ethylmaleimide, or iodoacetamide did not affect the S-oxidase activities, whereas solubilization of either hepatic or renal microsomes by cholate or heating of renal microsomes in the absence of NADPH significantly reduced the S-oxidase activities. In addition to male rat hepatic and renal microsomes, the S-oxidase activities were detected in lung microsomes of male rats and hepatic and renal microsomes of male mice and female rats and rabbits. The male rat kidney maintained the highest S-oxidase activity of all species and tissues examined. Whereas the aforementioned results provided further evidence for the S-oxidase activities being associated with FMOs, unambiguous evidence for this hypothesis was provided by the purification of the activities from rat liver (580-fold) and kidney (700-fold) microsomes and by the use of the isolated proteins in polyacrylamide gel electrophoresis, flavin content determinations, amino-terminal amino acid sequence analysis, amino acid composition analysis, and substrate kinetic studies. The findings that the S-oxidases were immunoreactive with antibodies raised against the pig liver 1A1 isozyme but not with antibodies raised against the rabbit lung 1B1 isozyme and that the liver S-oxidase amino-terminal amino acid sequence was more comparable to the amino-terminal amino acid sequences of pig and rabbit liver 1A1 isozymes than to those of rabbit lung 1B1 and liver 1D1 isozymes provide evidence that the S-oxidases are related to the known FMO 1A1 isozymes.
Mol Pharmacol 1993 Mar
PMID:Further characterization and purification of the flavin-dependent S-benzyl-L-cysteine S-oxidase activities of rat liver and kidney microsomes. 845 Aug 33

Purified rat pancreatic insulin-producing B-cells, which display a 12-fold higher activity of FAD-linked glycerophosphate dehydrogenase than other islet endocrine cells, were exposed for 30 min to 2 mM streptozotocin and subsequently cultured for 2 days in the absence or presence of 2 mM nicotinamide. Streptozotocin decreased by 54% the number of B-cells and, in surviving cells, lowered by 75% the activity of FAD-linked glycerophosphate dehydrogenase, whilst failing to affect that of glutamate dehydrogenase. This coincided with a 42-51% reduction of insulin secretion, when expressed relative to either the DNA or hormonal content of surviving cells. After exposure to streptozotocin, the presence of nicotinamide in the culture medium reduced cell death by 44% and also reduced the deleterious effects of streptozotocin upon both the enzymic and secretory activities of surviving cells. These findings indicate that the decreased activity of FAD-linked glycerophosphate dehydrogenase previously documented in pancreatic islets from streptozotocin-injected rats, as well as the protective effect of nicotinamide thereupon, are not attributable solely to changes in the number of B-cells but also to an altered enzymic activity in surviving B-cells. The latter anomaly may account, in part at least, for an impaired B-cell secretory response to D-glucose.
Mol Cell Biochem 1993 Mar 24
PMID:Effect of streptozotocin and nicotinamide upon FAD-glycerophosphate dehydrogenase activity and insulin release in purified pancreatic B-cells. 848 53

In several animal models of non-insulin-dependent diabetes, a decreased activity of FAD-linked glycerophosphate dehydrogenase was recently documented in pancreatic islet, but not liver, homogenates. The present study reveals that, on the contrary, the activity of the same mitochondrial enzyme is increased in islet, but not liver or spleen, homogenates of BB, as compared to BW, rats examined before the onset of severe hyperglycemia in this animal model of autoimmune insulin-dependent diabetes.
Biochem Mol Biol Int 1993 Feb
PMID:Increased activity of FAD-linked glycerophosphate dehydrogenase in pancreatic islets of BB rats. 849 19

Antisera to purified house fly NADPH-cytochrome P450 reductase were used to select cDNA clones from an expression library of abdomens of phenobarbital-treated house flies. A partial cDNA of 1841 bp containing a TAG termination codon, a consensus polyadenylation site and 269 bp of 3' untranslated sequence was obtained. Sequencing of a genomic clone coupled with mRNA sequencing yielded the complete coding sequence including the starting ATG. The resulting open reading frame of 2013 nucleotides codes for a protein of 671 residues. The native reductase apoprotein has a molecular weight of 76,366 and the deduced molecular weight of the holoenzyme (i.e. with 1 mol of FAD and FMN) is 77,608. The sequence of the house fly P450 reductase protein is highly similar to that of rabbit liver, the overall amino acid positional identity is 54.5% and the overall identity among eukaryotic P450 reductases is about 25%. The P450 reductase gene of 19-23 kb was located on chromosome III, as shown by comparison of RFLP-patterns of the P450 reductase gene in two house fly strains and their hybrids.
Insect Biochem Mol Biol 1993 Jun
PMID:The cDNA and deduced protein sequence of house fly NADPH-cytochrome P450 reductase. 850 86

We report the frequent occurrence in proteins of motifs consisting of either 9-membered or 11-membered rings that involve the side-chain amide groups of asparagine and glutamine residues. The syn CO and NH groups of these amide groups are hydrogen-bonded to the main-chain NH and CO groups of other amino acid residues. The main-chain part of both the 9-membered and 11-membered rings has the conformation of a beta-strand. One such ring motifs occurs, on average, in half of all the proteins we examined. Similar conformations are found for most examples of the 9-membered and 11-membered rings. One of the 11-membered rings is distinct, compared to the others, in that its main-chain part has a mirror-image conformation. Another of the 11-membered rings occurs at the interior of the variable domains of some antibodies and assists in linking the two beta-sheets. We observe one 9-membered ring structure in a dihydrofolate reductase complex in which the amide in the nicotinamide group of the ligand NADP is bound to the enzyme. Groups that can form hydrogen bonds in a similar way to amide groups occur in several nucleotide bases; we find one example of a 9-membered ring involving adenine and main-chain atoms in the FAD-protein complex of glutathione reductase. Both have conformations like those of the other 9-membered rings.
J Mol Biol 1993 Jun 05
PMID:Common ring motifs in proteins involving asparagine or glutamine amide groups hydrogen-bonded to main-chain atoms. 851 58


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