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)

Aryl sulfotransferase (AST) IV catalyzes the 3'-phosphoadenosine 5'-phosphosulfate-dependent sulfation of a variety of benzylic alcohols. Several molecular characteristics of benzylic alcohols were investigated for their ability to influence the catalytic efficiency of a homogeneous preparation of rat hepatic AST IV. The results of these studies indicated that lipophilicity of the benzylic alcohol was a major factor in determining catalytic efficiency, as represented by the values of kcat/Km. Furthermore, this effect was primarily mediated by a decrease in the apparent Km as a function of increasing lipophilicity of the molecules. This effect of lipophilicity was documented by a linear correlation between the apparent Km values of the benzylic alcohols and the logarithms of their octanol/water partition coefficients. In contrast to previously observed effects of para substituents on phenols, electronic effects of substituents on the phenyl ring had no effect on the catalytic efficiency of the enzyme with benzylic alcohols. In a further difference between phenol and benzylic alcohol substrates for AST IV, 2-naphthol exhibited pronounced substrate inhibition at pH 7.0, whereas the analogous benzylic alcohol, 2-naphthalenemethanol, did not. Stereochemistry at the benzylic carbon also had an effect on the catalytic efficiency of the AST IV; kcat/Km values for S-(-)-1-phenylethanol were approximately 3-fold higher than for R-(+)-1-phenylethanol.
Mol Pharmacol 1988 Apr
PMID:Sulfation of benzylic alcohols catalyzed by aryl sulfotransferase IV. 316 59

The purification to homogeneity and physical characterization of a monoamine-sulfating form of phenol sulfotransferase (PST) from human platelets is described. DEAE-cellulose chromatography of a 100,000 x g supernatant solution of homogenized human platelets revealed the presence of two peaks of both dopamine- and phenol-sulfating activity, termed M- and P-PST, respectively. The latter dopamine-sulfating form eluting from the ion exchange column, MII-PST, was purified approximately 10,000-fold to electrophoretic homogeneity by Sephacryl S-200 HR and 3'-phosphoadenosine-5'-phosphate-agarose chromatography. The final specific activity of the enzyme was 930 nmol/min/mg of protein. As determined by the hydrodynamic properties of MII-PST, the native Mr was approximately 69,000. The frictional ratio (f/fo) was estimated to be 1.28, indicating that the enzyme possesses a relatively low degree of asymmetry. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the affinity-purified enzyme revealed the presence of single Mr species of approximately 34,000, suggesting that MII-PST exists as a homodimer in vivo. Isoelectric focusing of purified MII-PST yielded a single protein species with a pl of 4.7. The sulfhydryl-modifying reagent N-ethylmaleimide (50 microM) was found to inactivate MII-PST in a time-dependent manner. This inactivation was totally prevented by saturating concentrations of 3'-phosphoadenosine-5'-phosphosulfate, whereas dopamine bestowed only partial protection to the enzyme. These results suggest that at least one sulfhydryl moiety is present at the active site of MII-PST.
Mol Pharmacol 1988 Aug
PMID:Physical characterization of a monoamine-sulfating form of phenol sulfotransferase from human platelets. 316 4

Plasmid pPGH1 originating from Pseudomonas putida strain H carries all the genes required for the degradation of phenol (or cresols) via the meta cleavage pathway. Besides mobilization of pPGH1 by a plasmid of the incompatibility group P-1, hybrid plasmids conferring the Phl+ phenotype could be selected, when R68.45 was the conjugative plasmid. The hybrids contain the complete R68.45 and part of pPGH1. Integration of Phl-DNA of pPGH1 into R68.45 occurred exclusively via the IS21 region of R68.45.
Mol Gen Genet 1988 Sep
PMID:In vivo generation of R68.45-pPGH1 hybrid plasmids conferring a Phl+ (meta pathway) phenotype. 322 24

In the family of ellipticine derivatives, those with an amino-phenol or a masked amino-phenol structure are among the most cytotoxic compounds. Preliminary studies on 9-hydroxy- or 9-methoxyellipticines have shown that these molecules behave as "pro-alkylating" agents. In order to rationalize the "biooxidative alkylation" process for various ellipticine derivatives, we report in the present article (i) their electrochemical oxidation parameters, (ii) their biochemical oxidation, (iii) the ability of the oxidized forms to form adducts with nucleophiles, (iv) the biological activities, and (v) the electronic properties of oxidized forms. We present some possible correlations between the oxidizability, the electrophilicity of the oxidized derivatives, and the biological activities of the corresponding drugs.
Mol Pharmacol 1988 Jan
PMID:The biooxidation of cytotoxic ellipticine derivatives: a key to structure-activity relationship studies? 333 51

Dot hybridization was used to detect specific rabies RNA in brains, either from experimental infection in mouse or from brain material to be processed for routine diagnosis. 32P cDNA probes were employed to identify minute amounts of specific viral RNA. Purified RNA was obtained after phenol extraction. The RNA was fixed on nylon membranes and hybridized with a pool of M13 inserts complementary to 200-400 nucleotides of each rabies gene and mRNA. Hybridized, labelled probes were detected by autoradiography. There was strong cross-hybridization between fixed rabies and street rabies virus RNA, which enable the detection of field strains for diagnosis purpose using a fixed rabies (PV strain) cDNA. A positive response was obtained with as little as 80 ng of brain RNA material from a fixed rabies-infected mouse. Detection of viral RNA was still specific 1 week after death, the brain material being left at room temperature. A total correlation was found when the samples were examined in parallel using a fluorescent rabies-specific antibody and by virus isolation on murine neuroblastoma cells. These data show that the use of rabies-specific cDNA probes in a dot-blot hybridization assay has great potential for the diagnosis of rabies.
Mol Cell Probes 1988 Mar
PMID:Rapid diagnosis of rabies infection by means of a dot hybridization assay. 338 Jan 7

Seventy-two chemicals were tested for their mutagenic potential in the L5178Y tk+/- mouse lymphoma cell forward mutation assay, using procedures based upon those described by Clive and Spector (Mutat Res 44:269-278, 1975) and Clive et al. (Mutat Res 59:61-108, 1979). Cultures were exposed to the chemicals for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 micrograms/ml. The chemicals were tested at least twice. Significant responses were obtained with allyl isothiocyanate, p-benzoquinone dioxime, benzyl acetate, 2-biphenylamine HCl, bis(2-chloro-1-methylethyl)ether, cadmium chloride, chlordane, chlorobenzene, chlorobenzilate, 2-chloroethanol, chlorothalonil, cytarabine.HCl, p,p'-DDE, diazinon, 2,6-dichloro-p-phenylenediamine, N,N-diethylthiourea, diglycidylresorcinol ether, 2,4-dimethoxy aniline.HCl, disperse yellow 3, endosulfan, 1,2-epoxyhexadecane, ethyl acrylate, ethyl benzene, ethylene thiourea, F D and C yellow Number 6, furan, heptachlor, isophorone, mercuric chloride, 4,4'-methylenedianiline.2 HCl, methyl viologen, nickel sulfate.6H2O, 4,4'-oxydianiline, pentachloroethane, piperonyl butoxide, propyl gallate, quinoline, rotenone, 2,4,5,6-tetrachloro-4-nitro-anisole, 1,1,1,2-tetrachloroethane, trichlorfon, 2,4,6-trichlorophenol, 2,4,5-trimethoxybenzaldehyde, 1,1,3-trimethyl-2-thiourea, 1-vinyl-3-cyclopetene dioxide, vinyl toluene, and ziram. Apart from 2-biphenylamine.HCl, 2-chloroethanol, disperse yellow 3, ethylene thiourea, FD and C yellow number 6, phenol, and 1,1,2-tetrachloroethane, rat liver S9 mix was not a requirement for these compounds. Chemicals not identified as mutagens were acid red, 11-aminoudecanoic acid, boric acid, 5-chloro-o-toluidine, coumaphos, cyclohexanone, decabromodiphenyl oxide, di(2-ethylhexyl)adipate, ferric chloride, fluometuron, melamine, monuron, phenesterin, phthalimide, reserpine, sodium dodecyl sulfate, 4,4-sulfonyldianiline, tetrachloroethylene, and zearalenone. The assay was incapable of providing a clear indication of whether some chemicals were mutagens; these were benzyl alcohol, 1,4-dichlorobenzene, phenol, succinic acid-2,2-dimethyl hydrazide, and toluene.
Environ Mol Mutagen 1988
PMID:Responses of the L5178Y tk+/tk- mouse lymphoma cell forward mutation assay: III. 72 coded chemicals. 338 42

It has recently been reported that phenol red, a pH indicator present in most tissue culture media, is a weak estrogen that can stimulate some estrogen-sensitive cells. However, the relative impact of phenol red on various cell lines is controversial. We examined the effect of phenol red on several estrogen-responsive cell systems that we use to study estrogen action. These included estrogenic stimulation of progesterone receptor and growth in human breast cancer-derived MCF-7 cells, stimulation of growth in human breast cancer-derived T47D cells, stimulation of prolactin synthesis in primary cultures of immature rat pituitary cells, and stimulation of progesterone receptor in primary cultures of immature rat uterine cells. Estrogenic responses in MCF-7 cells were the most sensitive to the presence of phenol red, while the other three cell cultures showed lesser effects of the indicator. In addition to intrinsic differences in cell responses, there were several other factors involved. These included differences in the estrogenic activity of phenol red-containing media and phenol red itself from different commercial suppliers, and differences in the concentration of free phenol red in final media due to binding of the indicator by serum. Higher concentrations of serum reduced the impact of phenol red on estrogenic responses in primary pituitary cells. Phenol red added to rat uterine cytosol competed with estradiol for binding to the estrogen receptor (relative binding affinity (RBA) approx. 0.001), and the acidic and basic forms of the indicator showed similar activity. Some commercial phenol red samples inhibited cell growth at levels of 100 mg/l; these effects were toxic rather than antiestrogenic, because growth inhibition could not be competitively reversed by an excess of estradiol. The amount of the indicator bound to serum in the final media, the source of the phenol red and the sensitivity of different cell types to the indicator ultimately determine its influence to the response of cells in tissue culture.
Mol Cell Endocrinol 1988 Jun
PMID:Estrogenic activity of phenol red. 340 60

The relations between the single high affinity binding sites for azapropazone, phenylbutazone, chlorpropamide, sulfathiazole, and iophenoxate and the binding regions of human serum albumin represented by the marker ligands diazepam, phenol red, salicylate, and warfarin were examined by a series of competition experiments. Binding was determined by equilibrium dialysis at pH 7.0. In order to ensure an accurate analysis of the competition experiment, the number of moles of ligand bound per mole of protein was usually 0.4 or less to minimize ligand binding to weaker sites. Furthermore, binding of both ligands was determined in all experiments (except for iophenozate). None of the test ligands competed with diazepam for a common high affinity binding site, but, surprisingly, they were all able to displace two or three of the other marker ligands according to a competitive scheme. These findings show, first, the existence of a particular serum albumin region for high affinity binding of diazepam. Secondly, they imply that it is not necessary to assume the existence of new drug binding regions beyond those existing for phenol red, salicylate, and warfarin. On the contrary, the relatively many examples of competitive binding indicate that the binding regions represented by the last-mentioned three marker ligands are placed quite close to each other in the albumin molecule in a common region, which is suggested to be located at subdomains 1C and 2A-B. The region must be relatively large, because in some cases independent high affinity binding of pairs of ligands is observed. It is probably also rather flexible, inasmuch as no clear relation could be found between the chemical structure of the test ligands and the two or three marker ligands with which they compete. Correlations between primary association constants and partition coefficients for both marker ligands and test ligands, in the unionized forms, between n-hexane or 1-octanol and aqueous media showed that hydrophobic forces are important for the binding processes. However, the data also showed that other attractive forces must be operative as well.
Mol Pharmacol 1988 Aug
PMID:Evidence for a large and flexible region of human serum albumin possessing high affinity binding sites for salicylate, warfarin, and other ligands. 341 20

The acid-insoluble product isolated from well-oxygenated Langendorff rat heart after perfusion with [14C]adenosine was purified by phenol extraction and subjected to specific phosphorolysis by pure polynucleotide phosphorylase. TLC analysis of the reaction mixture showed that ADP was the only radioactive product, proving that the original substance was a polyribonucleotide. Studies of the time course of labelling and of the distribution of the acid-insoluble product between the mitochondrial and nuclear fractions showed that both are labelled even after 1 min at 25 degrees C, but at short times and low temperature more radioactivity is found in the mitochondria. The kinetics of adenosine incorporation resemble those expected for the labelling of hnRNA and mRNA. Isolated, respiring mitochondria incorporate adenosine and adenine nucleotides into acid insoluble form by a process dependent on oxidative phosphorylation and the adenine nucleotide translocase that is specific for adenine derivatives. The results are discussed in terms of the hypothesis that the polyribonucleotide might be a storage form of adenine nucleotides: it is concluded that the bulk of the labelled product is unlikely to play a major role in energy metabolism.
Mol Cell Biochem 1987 Nov
PMID:Studies of adenosine incorporation in Langendorff rat heart and rat heart mitochondria. 345 67

Using computer-aided molecular modeling techniques to analyze models recently proposed for the receptor binding sites of dopaminergic agonists, we superimposed the chemical structures of various compounds that mimic the pharmacological behavior of dopamine, as well as inactive enantiomers, on a postulated three-dimensional frame of reference. We analyzed the vector directionalities of the lone pairs of the nitrogen common to these molecules, and the acidic hydrogen of phenols (in aminoindanes, aminotetralins, apomorphines, p-phenol-piperazines, octahydrobenzo(g)quinolines, octahydrobenzo(f)quinolines, and benzazepines) or of nitrogen (in ergoline-type compounds and related structures). This model, when expressed as distances from that of the reference compound pergolide, correlates with the dopaminergic binding affinity observed in compounds previously reported to act on the dopaniergic system in the central nervous system (CNS). The regression analysis of log KD with respect to the distances of the vectors of the acidic hydrogen support the hypothesis that these compounds bind to the receptor as donors in hydrogen bond formation.
J Comput Aided Mol Des 1987 Jul
PMID:Computer-aided molecular modeling of a D2-agonist dopamine pharmacophore. 350 12


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