Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: HUMANGGP:026099 (oxidoreductase)
 7,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When modified by 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl (TMPO) bovine liver glutamate dehydrogenase (L-glutamate NAD(P) oxidoreductase, E. C. 1.4.1.3) looses its catalytical activity and sensitivity to allosteric inhibitor GTP. The stoicheiometry of the binding of TMPO to glutamate dehydrogenase has been studied--each protomer bound one molecule of TMPO. It is supposed that TMPO reacts with lysine residue located in the enzyme's active center.
 ...
PMID:[Bovine liver glutamate dehydrogenase modified by 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl: enzymatic activity and catalytic properties]. 707 Mar 87

6-Phosphogluconate dehydrogenase (6-phospho-D-gluconate: NADP+ 2-oxidoreductase(decarboxylating), EC 1.1.1.44) from Candida utilis is inhibited by reaction with pyridoxal 5'-phosphate. The aldehydic group of this compound forms a Schiff base with the epsilon-amino group of a lysine residue: reduction of this enamine with tritiated borohydride can label this amino acid. Two tryptic peptides, TS2 and TS3, have been isolated from the labelled protein and found to have the following amino acid sequences: TS2: Ile-Leu-Asx-Glx-Ala-Gly-Gly-Lys(P-Pxy)-Gly-Glx-Thr-Lys TS3: Thr-Val-Ser-Lys(P-Pxy)-Val-Asp-His-Phe-Ile-(Glx,Asx,Glx)-Ala-Lys where Lys(P-Pxy) indicates the modified lysine residue. The similarities between the amino acid sequences around the pyridoxal phosphate binding lysines of 38 peptides, obtained from enzymes which have pyridoxal phosphate as cofactor or inhibitor, are discussed and a prediction is made on the presence of reverse turns in these peptides.
 ...
PMID:Amino acid sequence around the pyridoxal 5'-phosphate binding sites of 6-phosphogluconate dehydrogenase. 719 16

1. The sites of chymotrypsin action on glyceraldehyde 3-phosphate dehydrogenase (D-glyceraldehyde 3-phosphate) : DNA+ oxidoreductase (phosphorylating), EC 1.2.1.12) was established; limited proteolysis by chymotrypsin results in lowering of the phosphorolytic activity of the enzyme without affecting its oxidative activity. 2. The low-molecular fraction of the chymotrypsin digest separated by Sephadex G-100 chromatography, was fractionated on Bio-gels. Determination of the amino acid composition of the nine peptides isolated, and of their amino acid sequence, permitted to relate cleavage of Leu-64, Trp-84, Leu-109, Leu-141, Phe-165, Lys-212, Val-239, Leu-242, Leu-271 (or Phe-315) bonds in the enzyme to the decrease of the phosphorolytic activity.
 ...
PMID:The sites of chymotrypsin action on the pig muscle glyceraldehyde 3-phosphate dehydrogenase during limited proteolysis. 726 78

We isolated the cDNA of a novel protein disulfide isomerase (PDI)-related protein, designated PDIR, from a human placental cDNA library. Deduced from its nucleotide sequence, PDIR has the three CXXC-like motifs (Cys-Ser-Met-Cys, Cys-Gly-His-Cys and Cys-Pro-His-Cys), which are found in proteins within the PDI superfamily and are responsible for oxidoreductase activity. PDIR has a hydrophobic stretch at its amino terminus, which may serve as a signal sequence, and the putative endoplasmic reticulum (ER) retention signal 'Lys-Glu-Glu-Leu' at its carboxy terminus, indicating that PDIR is an ER resident protein. Northern blots showed that PDIR is preferentially expressed in cells actively secreting proteins and that the expression of PDIR is stress-inducible. These results suggested that PDIR has oxidoreductase activity of disulfide bonds against polypeptides and that it acts as a catalyst of protein folding in the lumen of the ER.
 ...
PMID:Molecular cloning of the cDNA encoding a novel protein disulfide isomerase-related protein (PDIR). 755 71

NAD(P)H: quinone-acceptor oxidoreductase (EC 1.6.99.2), also referred to as DT-diaphorase, is a flavoprotein that catalyzes the two-electron reduction of quinones and quinonoid compounds to hydroquinones, using either NADH or NADPH as the electron donor. Using an Escherichia coli expression system developed previously, we prepared three mutants of the rat liver quinone reductase. These mutants are Lys-113-His (K113H), Lys-113-Asp (K113D), and Lys-113-Ala (K113A). While the mutant K113H was readily purified using the same procedure as for the purification of the wild-type quinone reductase and found to have an activity similar to that of the wild-type enzyme, K113D and K113A were purified only in very small quantities, mainly in the form of apoprotein, and had very low activities. The results suggest that a positively charged amino acid at this position is important for the binding of the flavin adenine dinucleotide (FAD) prosthetic group. Flavin spectral studies of 6-mercapto-FAD-reconstituted mutants revealed that mutation at Lys-113 affects the protein environment around position-6 of the isoalloxazine ring.
 ...
PMID:A site-directed mutagenesis study at Lys-113 of NAD(P)H:quinone-acceptor oxidoreductase: an involvement of Lys-113 in the binding of the flavin adenine dinucleotide prosthetic group. 763 39

The complete amino acid sequence of a low molecular weight peptide from the hemolymph of the housefly Musca domestica L., which had been determined to competitively inhibit phenol oxidase (PO; monophenol, dihydroxy-phenylalanine:oxygen oxidoreductase; EC 1.14.18.1) in the nM range, was unambiguously established by employing both automatic Edman degradation and mass spectrometry. The physiologically active peptide, which was designated phenol oxidase inhibitor (POI), has an observed molecular weight of 4213.1 +/- 0.2 by electrospray ionization mass spectrometry. The relatively short and structurally dense peptide contained 38 amino acid residues rich in cysteine and lysine. Comparison of the observed and calculated molecular mass indicates that apparently all six cysteine residues form disulfide bridges. Interestingly, sequence analyses of both the intact and protease-digested S-pyridylethylated POI showed that one of the two tyrosine residues (Tyr-32) is hydroxylated to a 3,4-dihydroxyphenylalanine (dopa) residue. This agreed with the increase of 16 mass units observed in mass spectrometric measurements. This was further verified by submission of free L-dopa to the sequencer, which gave a retention time consistent with the atypical peak observed at the Edman cycle of the peptide containing dopa. This study demonstrates the existence of a biologically active, dopa-containing peptide among the insects. Since the POI activity was most prominent in aged pupae, especially pharate adults, the POI may play an important role in smoothing the way of adult emergence through hindering excessive melanization, as well as hardening, of cuticular proteins under the epicuticle.
 ...
PMID:Primary structure of a potent endogenous dopa-containing inhibitor of phenol oxidase from Musca domestica. 770 56

A Pseudomonas sp. soil strain, selected for its ability to grow on epsilon-(1-deoxyfructosyl) aminocaproic acid, was induced to express a membrane-bound enzymatic activity which oxidatively degrades Amadori products into free fructosamine. Apparent Km values for fructosyl aminocaproate, epsilon-fructosyl lysine, fructosyl glycine, and ribated lysine were 0.21 mM, 2.73 mM, 3.52 mM, and 1.57 mM, respectively. The enzyme was also active against alpha-fructosyl lysine and borohydride-reduced Amadori product, weakly active with ribated and glycated polylysine, and inactive with reducing sugars, amino acids, and glycated proteins. The enzymatic activity was highest at pH 6.5 and 25 degrees C in 0.1 M sodium phosphate, while over 80% of the activity was lost above 65 degrees C. Complete inhibition was observed by HgCl2, NaN3, and NaCN suggesting a role for SH groups and copper in the enzymatic activity. The reaction products were characterized by 1H NMR, 13C NMR, and GC/MS and found to correspond to 1-deoxy-1-aminofructose, i.e. free "fructosamine," and adipic acid. Confirmation of the free fructosamine structure was based on the complete spectroscopic identity of the borohydride reduction product with commercially available glucamine (1-amino-1-deoxyglucitol). The new enzyme is provisorily classified as fructosyl N-alkyl amino acid oxidase (EC 1.5.3) (fructosyl-amino acid:oxygen oxidoreductase) and may thus belong to a novel class of "Amadoriases" which deglycate Amadori products oxidatively. In contrast, however, the new enzyme acts on the alkylamine bond rather than the ketoamine bond of the Amadori product.
 ...
PMID:Novel degradation pathway of glycated amino acids into free fructosamine by a Pseudomonas sp. soil strain extract. 781 78

The widespread occurrence of Pro residues adjacent to Cys ligands in the sequences of [4Fe-4S] electron transfer proteins has not yet found a functional basis. The two such Pro of Clostridium pasteurianum 2[4Fe-4S] ferredoxin have been probed by site-directed mutagenesis. Any one of them, but not both simultaneously, can be substituted without impairing the proper folding of the protein. The reduction potentials of the ferredoxin variants fall in a narrow range of < 20 mV above the potential of the native protein. The biological activities with C. pasteurianum hydrogenase and pyruvate-ferredoxin oxidoreductase do not change significantly, except when Lys replaces Pro. In these cases, the data suggest that the two clusters of 2[4Fe-4S] ferredoxin may not always be equivalent in the interaction with the redox partners. Destabilization of the structure has been observed as the consequence of the Pro19 or Pro48 substitutions. Using 2-D NMR, this effect has been associated with perturbations of both the hydrogen bond network and one amino acid side chain around the [4Fe-4S] clusters. Thus, the conserved Pro found in the binding motif of [4Fe-4S] clusters in proteins strongly stabilizes the active site but does not play an essential role in the mechanism of electron transfer.
 ...
PMID:On the role of conserved proline residues in the structure and function of Clostridium pasteurianum 2[4Fe-4S] ferredoxin. 807 38

Complementary DNA (cDNA) clones encoding bovine testicular 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) have been isolated from a bovine testicular lambda gt11 library using polyclonal antibodies against 20 alpha-HSD and DNA probe hybridization. Nucleotide sequencing of three independently isolated clones was used to establish a composite cDNA sequence that encodes the enzyme. It contains a coding sequence of 921 nucleotides, a stop codon, and a 264-nucleotide 3'-noncoding segment which allowed deduction of the amino acid sequence of the enzyme. A computer homology search of the 20 alpha-HSD cDNA performed against the GenBank DNA sequence database revealed it to be identical with bovine lens aldose reductase (alditol:NADPH oxidoreductase; EC 1.1.1.21), and a literature search reveals the deduced amino acid sequence to be identical with that reported for the bovine enzyme. Sequences obtained from the N-terminus of purified testicular 20 alpha-HSD and from random peptides obtained by treatment with endopeptidase Lys-C are all identical with regions of the deduced amino acid sequence of 20 alpha-HSD and/or the published sequence of aldose reductase. Further, the enzyme purified to homogeneity by following activity with 17-hydroxyprogesterone as a substrate was shown to reduce glucose, glyceraldehyde, and benzaldehyde (all classic aldose reductase substrates). Finally, 17-hydroxyprogesterone inhibited the reduction of benzaldehyde and glyceraldehyde. Because aldose reductase has been implicated in the etiology of diabetic complications, acceptance of steroid substrates may offer new implications for therapy.
 ...
PMID:Molecular cloning of testicular 20 alpha-hydroxysteroid dehydrogenase: identity with aldose reductase. 843 20

We report the structure of an NADPH:FMN oxidoreductase (flavin reductase P) that is involved in bioluminescence by providing reduced FMN to luciferase. The 1.8 A crystal structure of flavin reductase P from Vibrio harveyi was solved by multiple isomorphous replacement and reveals that the enzyme is a unique dimer of interlocking subunits, with 9352 A2 of surface area buried in the dimer interface. Each subunit comprises two domains. The first domain consists of a four-stranded antiparallel beta-sheet flanked by helices on either side. The second domain reaches out from one subunit and embraces the other subunit and is responsible for interlocking the two subunits. Our structure explains why flavin reductase P is specific for FMN as cofactor. FMN is recognized and tightly bound by a network of 16 hydrogen bonds, while steric considerations prevent the binding of FAD. A flexible loop containing a Lys and an Arg could account for the NADPH specificity. The structure reveals information about several aspects of the catalytic mechanism. For example, we show that the first step in catalysis, which is hydride transfer from C4 of NADPH to cofactor FMN, involves addition to the re face of the FMN, probably at the N5 position. The limited accessibility of the FMN binding pocket and the extensive FMN-protein hydrogen bond network are consistent with the observed ping-pong bisubstrate--biproduct reaction kinetics. Finally, we propose a model for how flavin reductase P might shuttle electrons between NADPH and luciferase.
 ...
PMID:Flavin reductase P: structure of a dimeric enzyme that reduces flavin. 888 32


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>