Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The X-ray structure analyses of four glutathione reductase complexes and derivatives have been extended to 2 A resolution and refined. The results are discussed in conjunction with the structure of the oxidized native enzyme known at 1.54 A resolution. While the residual co-ordinate errors are around 0.2 A, some significant shifts even in this range could be established. Points of particular interest are the 3.2 A approach of C4N of nicotinamide to N5F of flavin in hydride transfer geometry, the hydrogen bond geometries of the 2'-phosphate of NADPH as compared to inferior geometries for an inorganic phosphate binding together with NADH, the differential mobilities of parts of the substrates as derived from refined atomic temperature factors, and the stabilization of the thiolate of the proximal Cys63 by conformational changes of neighboring residues as well as by flavin. In addition, catalytically competent His467' is seen to interact more optimally with the sulfur of glutathione-I than with the distal sulfur of Cys58. The observed participation of water molecules for both NADPH and glutathione binding is so extensive that a prediction of the binding mode merely from the polypeptide structure would be very difficult. The accurately known geometries allowed us to draw some conclusions on the enzyme mechanism and suggest a possible scenario of the catalysis.
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PMID:Substrate binding and catalysis by glutathione reductase as derived from refined enzyme: substrate crystal structures at 2 A resolution. 258 16

7B2 is a novel neuroendocrine polypeptide which belongs to an entirely new superfamily of proteins. In extension of previous reports on 7B2, these studies concern its expression in endocrine pancreatic tissue. They have been performed using specific antibodies prepared against two distinct synthetic fragments of 7B2 comprising amino acids 23-39 and 117-128 of the native human molecule isolated from pituitary gland. Pancreatic insulin-secreting tumors produced in transgenic mice contain high amounts of 21,500- to 22,000-dalton forms of 7B2. Using light microscopy (immunocytochemical colocalization with different pancreatic hormones), immunoreactivity to 7B2 (IR-7B2) was consistently found within cells producing insulin and glucagon and less consistently within pancreatic polypeptide-containing cells. As in previous reports concerning the brain, adenohypophysis, and thyroid gland, IR-7B2 could be detected by electron microscopy within secretory granules of alpha- and beta-like cells in islets. Furthermore, the IR-7B2 level was higher in extracts of insulin-producing tumors of the transgenic mice that contained the hybrid insulin II gene. In addition, IR-7B2 could be detected immunocytochemically in three of seven tumors produced in the rat by streptozotocin-nicotinamide treatment.
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PMID:Secretory protein 7B2 is associated with pancreatic hormones within normal islets and some experimentally induced tumors. 284 Feb 70

Clostridium perfringens type E iota toxin is composed of two separate and independent polypeptide chains that act synergistically in mouse lethal assays. The light chain is an enzyme that mono(ADP-ribosyl)ates certain amino acids. The enzyme displays substantial activity when homopoly-L-arginine is used as a substrate, but it shows little activity when polyasparagine, polylysine or polyglutamic acid are used. In keeping with the properties of an ADP-ribosylating enzyme, the toxin possesses the following characteristics. It produces incorporation of radioactivity into polyarginine when adenine-labeled NAD is used, but radioactivity is not incorporated when nicotinamide-labeled NAD is used. Irrespective of labeling, enzymatic activity is accompanied by the release of free nicotinamide. After incorporation of ADP-ribose groups into polyarginine, enzymatic and chemical techniques can be used to release the incorporated material. Snake venom phosphodiesterase releases mainly AMP; hydroxylamine releases AMP and ADP-ribose. The heavy chain of iota toxin has little or no enzyme activity, and it does not substantially affect the enzyme activity of the light chain. The heavy chain may be a binding component that directs the toxin to vulnerable cells. The data suggest that iota toxin is a representative of a novel class of ADP-ribosylating toxins.
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PMID:Molecular basis for the pathological actions of Clostridium perfringens iota toxin. 287 81

Complex I (nicotinamide adenine dinucleotide-ubiquinone reductase) is a complex enzyme system located in the inner mitochondrial membrane. It has the ability to catalyze several different enzymatic reactions in electron transport, and is known to be one of the respiratory chain components most sensitive to ischaemia. Mitochondria and two complexes I (complex IA and complex IB) were isolated from normal and ischaemic myocardial tissue. Enzymatic activities, polypeptide composition, as well as other components such as non-haem iron, acid-labile sulphur and ubiquinone, were determined. The results indicated that complex IB reflected the enzymatic changes in the mitochondria during myocardial ischaemia, but complex IA did not. The lesion that resulted from ischaemia was localised as altered enzymatic activities due to a different polypeptide composition, as well as loss of ubiquinone and non-haem iron from complex IB.
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PMID:Enzymatic and structural modifications of mitochondrial NADH-ubiquinone reductase with autolysis as experimental model. 289 5

Replication of vaccinia virus (VV) in monolayers of BSC40 cells was inhibited 99.9% in the presence of 60 mM nicotinamide (NIC), a competitive inhibitor of ADP-ribosylation reactions. Dot-blot hybridization analysis of infected cell extracts utilizing a VV DNA-specific probe indicated that the drug had only minimal effects on viral DNA synthesis. SDS-polyacrylamide gel electrophoresis of newly synthesized VV proteins pulse-labeled at early (2 h) or late (8 h) times post-infection revealed that although the full spectrum of expected viral polypeptides was evident, quantitative differences in the levels of expression of a distinct subset of viral proteins were observed in the presence of the drug. Velocity sedimentation of virus-infected cell lysates established that no mature particles were assembled in drug treated cells. Additional evidence suggesting that VV morphogenesis was abortive in the presence of NIC was obtained by pulse-chase labeling experiments that demonstrated that the two VV major late core polypeptide precursors P94 and P65, whose proteolytic processing to VP62 and VP60 is intimately associated with viral assembly, were not cleaved in the presence of NIC. Interestingly, growth of VV in the presence of [3H]adenosine resulted in the metabolic labeling of eight proteins that were associated with purified virions. These proteins co-migrated with proteins labeled with [3H]adenosine that were present in extracts of VV-infected, but not uninfected, cells. These analyses also revealed that the [3H]adenosine-labeling of a subset of cellular proteins (MW 18-20 kDa, possibly histones) was increased 4-fold by VV infection. The observed induction of either increased synthesis or hyper-modification of these 18-20 kDa proteins was inhibited by NIC. These results are discussed with respect to whether one or more VV polypeptides are subject to obligatory ADP-ribosylation modification reactions in order to attain their active configuration, and if so, whether the enzymes catalyzing these reactions are specified by the virus or host cell.
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PMID:Inhibition of vaccinia virus replication by nicotinamide: evidence for ADP-ribosylation of viral proteins. 296 68

The enzyme that catalyzes the ADP-ribosylation and concomitant inactivation of dinitrogenase reductase in Rhodospirillum rubrum has been purified greater than 19,000-fold to near homogeneity. We propose dinitrogenase reductase ADP-ribosyltransferase (DRAT) as the working name for the enzyme. DRAT activity is stabilized by NaCl and ADP. The enzyme is a monomer with a molecular mass of 30 kDa and is a different polypeptide than dinitrogenase reductase activating glycohydrolase. NAD (Km = 2 mM), etheno-NAD, nicotinamide hypoxanthine dinucleotide, and nicotinamide guanine dinucleotide will serve as donor molecules in DRAT-catalyzed ADP-ribosylation reaction, and dinitrogenase reductases from R. rubrum, Azotobacter vinelandii, Klebsiella pneumoniae, and Clostridium pasteurianium will serve as acceptors. No other proteins or small molecules, including water, have been found to be effective as acceptors. Nicotinamide is released stoichiometrically with formation of the ADP-ribosylated product. DRAT is inhibited by NaCl and has maximal activity at a pH of 7.0.
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PMID:Purification and properties of dinitrogenase reductase ADP-ribosyltransferase from the photosynthetic bacterium Rhodospirillum rubrum. 314 11

The gene coding for cyclohexanone monooxygenase from Acinetobacter sp. strain NCIB 9871 was isolated by immunological screening methods. We located and determined the nucleotide sequence of the gene. The structural gene is 1,626 nucleotides long and codes for a polypeptide of 542 amino acids; 389 nucleotides 5' and 108 nucleotides 3' of the coding region are also reported. The complete amino acid sequence of the enzyme was derived by translation of the nucleotide sequence. From a comparison of the amino acid sequence with consensus sequences of nucleotide-binding folds, we identified a potential flavin-binding site at the NH2 terminus of the enzyme (residues 6 to 18) and a potential nicotinamide-binding site extending from residue 176 to residue 208 of the protein. An overproduction system for the gene to facilitate genetic manipulations was also constructed by using the tac promoter vector pKK223-3 in Escherichia coli.
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PMID:Acinetobacter cyclohexanone monooxygenase: gene cloning and sequence determination. 333 74

Beef liver and human erythrocyte catalases (EC 1.11.1.6) bind NADP tenaciously [Kirkman, H. N. & Gaetani, G. F. (1984) Proc. Natl. Acad. Sci. USA 81, 4343-4348]. The position of NADP on beef liver catalase corresponds to the carboxyl-terminal polypeptide hinge in Penicillium vitale fungal catalase, which connects the common catalase structure to the additional flavodoxin-like domain. In contrast to nearly all other known structures of protein-bound NADP, NAD, and FAD, the NADP molecule of beef liver catalase is folded into a right-handed helix and bound, in part, in the vicinity of the carboxyl end of two alpha-helices. A water molecule (W7) occupies a pseudosubstrate site close to the C4 position of the nicotinamide and is hydrogen bonded to His-304. Although the NADP and heme groups approach each other to within 13.7 A, there is no direct interaction. The function of the NADP remains a mystery.
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PMID:The NADPH binding site on beef liver catalase. 385 39

Pig heart mitochondrial malate dehydrogenase (EC 1.1.1.37), which has been obtained free of electrophoretic subforms, has been shown to have a molecular weight of 67,000 and to be composed of two polypeptide chains. Comparison of these and other properties, such as amino-acid composition, isoelectric point, and keto-substrate inhibition, with those of (L)-3-hydroxyaeyl CoA dehydrogenase (EC 1.1.1.35), another NAD(+)-dependent dehydrogenase of mitochondrial origin, suggests structural similarities of the type associated with proteins possessing common evolutionary origins. This conclusion is supported by immunological crossreactivity. In view of these observations, the dissimilarity in the stereospecificity of hydrogen transfer from cofactor to substrate catalyzed by the two enzymes is attributed to 180 degrees rotation in the binding orientation of the nicotinamide moiety of the NAD(+), rather than to gross differences in the geometry of the active site of the two enzymes.
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PMID:Structural and functional similarities between mitochondrial malate dehydrogenase and L-3-hydroxyacyl CoA dehydrogenase. 413 51

Micrococcus aerogenes grown in media containing glutamate has high levels of glutamate dehydrogenase and alpha-ketoglutarate reductase. The latter enzyme catalyzes the reversible reduction of alpha-ketoglutarate to alpha-hydroxyglutarate in the presence of reduced nicotinamide adenine dinucleotide (NADH). The enzyme has a high specificity for both substrates in either direction and displays Michaelis-Menten kinetics at moderate substrate concentrations. K(m) values of 0.12 to 0.17 mm alpha-ketoglutarate and 0.3 mm NADH for the forward reaction were calculated from data obtained at low substrate concentrations. At high concentrations, this reaction was inhibited by both substrates. The reverse reaction, which proceeded at 0.1 to 0.2 times the rate of the forward reactions, was inhibited by one of the products, alpha-ketoglutarate. K(m) values for the substrates of this reaction were 10 mm for alpha-hydroxyglutarate and 1 mm for nicotinamide adenine dinucleotide. alpha-Ketoglutarate reductase has a molecular weight of 7.5 x 10(4) to 8.2 x 10(4) and is composed of identical polypeptide chains with a molecular weight of 3.6 x 10(4) to 3.8 x 10(4).
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PMID:Purification and properties of alpha-ketoglutarate reductase from Micrococcus aerogenes. 439 93


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