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)

Ivermectin is a member of the avermectin family of compounds that are used to treat helminth and arthropod diseases in humans, domestic animals, and plants. A membrane-bound high affinity ivermectin binding site was extracted from Caenorhabditis elegans with the nonionic detergent 1-O-n-octyl-beta-D-glucopyranoside. The free-living nematode C. elegans is highly sensitive to the avermectins and was used as a model of parasitic nematodes. The membrane-bound and detergent-solubilized ivermectin binding sites are stable and exhibit high affinity binding, with dissociation constants of 0.11 nM and 0.20 nM, respectively. The maximum binding of [3H]ivermectin is 0.54 pmol/mg of membrane protein and 0.66 pmol/mg of detergent-soluble protein. Kinetic analysis of ivermectin binding shows that the ivermectin binding sites form a slowly reversible complex with ivermectin. The rates of dissociation of [3H]ivermectin with the solubilized and membrane-bound binding sites are 0.005 min-1 and 0.006 min-1, respectively. The association rate of the soluble binding site is 0.053 nM-1 min-1, slightly slower than that observed for the membrane-bound site, 0.074 nM-1 min-1. To characterize the ivermectin binding site, competition experiments were performed by inhibiting [3H]ivermectin binding with several avermectin derivatives and the neurotransmitter gamma-aminobutyric acid (GABA). The order of potency was 22,23-dihydroavermectin B1a monosaccharide greater than 22,23-dihydroavermectin B1a aglycone greater than 3,4,8,9,10,11,22,23-octahydro B1 avermectin for both the membrane-bound and NOG-soluble binding sites. GABA did not compete with ivermectin binding, although it has been suggested that ivermectin acts at the GABA-gated chloride channel in some invertebrate systems. Optimum ivermectin binding and assay conditions have been determined. The detergent-soluble ivermectin binding site appears to be negatively charged and has a pl of 4.0 and an apparent Mr in Triton X-100 micelles of 340,000. Detergent solubilization of a high affinity ivermectin binding site will enable the subsequent purification and characterization of a putative site of ivermectin action.
Mol Pharmacol 1991 Aug
PMID:Solubilization and characterization of a high affinity ivermectin binding site from Caenorhabditis elegans. 187 15

The selective distribution of methionyl aminopeptidase (MAP) among rat liver mitochondria (heavy and light) and microsomes is reported. Several properties of MAP from the three subcellular fractions showed that the enzyme is a typical aminopeptidase able to remove N-terminal methionine from oligopeptides and methionyl-2-naphthylamide but not from Met-Ala-Ser. MAP is a membrane-bound enzyme sensitive to SH-group oxidants and inhibitable by L-methionine but not by usual arylaminopeptidase inhibitors. It is suggested that, MAP may play an important role during protein synthesis in rat liver.
Mol Cell Biochem 1991 Apr 10
PMID:Methionyl aminopeptidase from rat liver: distribution of the membrane-bound subcellular enzyme. 188 86

Calpains and calpastatin in the brain of the rabbit were examined in experimental situations that could mimic some features of brain ischemia. Incubations of bisected brains in saline at 39 degrees C for 0.5, 1, or 1.5 h resulted in a decreased calpain I activity in the cytosol and in an increased hydrophobicity of cytosolic calpain II activity. Incubation of brain homogenates at different pH levels demonstrated an almost-complete transfer of calpains from the cytoplasmic compartment to the membranes when pH was lowered from 6 to 5. At pH values lower than 5, the total calpain activity (soluble plus membrane-bound) markedly decreased. No significant changes of calpastatin activity or its subcellular distribution was found following incubation of the homogenates at different pH levels.
Mol Chem Neuropathol 1991 Apr
PMID:Changes in brain calpain activity as a result of in vitro ischemia and pH alterations. 191 Mar 62

Ultrastructural evidence is presented for the presence of membrane-bound glucocorticoid recognition and binding sites. Corticosterone was derivatized at 3 different positions and coupled covalently to bovine serum albumin (BSA). All three derivatives competed for binding of [3H]corticosterone by isolated rat hepatocytes. The most effective competitor, corticosterone-succinate-BSA (CSB), was adsorbed onto colloidal gold particles (CSB-gold, 17 +/- 3 nm dia). When isolated rat hepatocytes or mouse pituitary tumor cells (AtT 20) are incubated with CSB-gold, specific binding in the microvilli-rich region of these cells is seen. This binding of CSB-gold is reduced by about 50% in the presence of unlabelled CSB or corticosterone.
J Steroid Biochem Mol Biol 1991 Sep
PMID:Electron microscopic demonstration of glucocorticoid recognition sites on isolated rat hepatocytes. 191 20

Glucose is taken up in Bacillus subtilis via the phosphoenolpyruvate:glucose phosphotransferase system (glucose PTS). Two genes, orfG and ptsX, have been implied in the glucose-specific part of this PTS, encoding an Enzyme IIGlc and an Enzyme IIIGlc, respectively. We now show that the glucose permease consists of a single, membrane-bound, polypeptide with an apparent molecular weight of 80,000, encoded by a single gene which will be designated ptsG. The glucose permease contains domains that are 40-50% identical to the IIGlc and IIIGlc proteins of Escherichia coli. The B. subtilis IIIGlc domain can replace IIIGlc in E. coli crr mutants in supporting growth on glucose and transport of methyl alpha-glucoside. Mutations in the IIGlc and IIIGlc domains of the B. subtilis ptsG gene impaired growth on glucose and in some cases on sucrose. ptsG mutants lost all methyl alpha-glucoside transport but retained part of the glucose-transport capacity. Residual growth on glucose and transport of glucose in these ptsG mutants suggested that yet another uptake system for glucose existed, which is either another PT system or regulated by the PTS. The glucose PTS did not seem to be involved in the regulation of the uptake or metabolism of non-PTS compounds like glycerol. In contrast to ptsl mutants in members of the Enterobacteriaceae, the defective growth of B. subtilis ptsl mutants on glycerol was not restored by an insertion in the ptsG gene which eliminated IIGlc. Growth of B. subtilis ptsG mutants, lacking IIGlc, was not impaired on glycerol. From this we concluded that neither non-phosphorylated nor phosphorylated IIGlc was acting as an inhibitor or an activator, respectively, of glycerol uptake and metabolism.
Mol Microbiol 1991 May
PMID:The glucose permease of the phosphotransferase system of Bacillus subtilis: evidence for IIGlc and IIIGlc domains. 195 1

We purified the high-molecular-weight perforin inhibitor protein from normal human serum using DEAE-cellulose, HPLC-gel filtration and hydroxylapatite chromatography. This protein was shown to be identical to the serum apolipoprotein B-100 in terms of amino acid composition and the sequence of the digested peptides. This inhibitor protein not only inhibits the membrane binding activity of perforin but also the pore insertion activity of membrane-bound perforin.
Mol Immunol 1991 Nov
PMID:Apolipoprotein B is a major perforin inhibitor protein in human serum. 196 Nov 97

Murine T cells synthesize and express a cell-surface glycophospholipid anchored 40 kDa and a secreted water-soluble 39 kDa Qa-2 polypeptide. We have examined the biosynthetic pathways which lead to the production of the membrane-bound and water-soluble isoforms of the Qa-2 molecule. Using the detergent TX-114, both detergent (membrane)-bound and soluble Qa-2 polypeptides can be identified in cell lysates and can be distinguished by charge and molecular weight. Two membrane-bound forms, a 40-kDa Endo H resistant cell-surface form and a 38 kDa-Endo H sensitive form can be identified, both of which can be biosynthetically labeled with 3H-ethanolamine and can be converted to water soluble forms by digestion with a phosphatidylinositol specific phospholipase C. In addition, several water soluble polypeptides at 39, 37, 35 kDa, and a minor species at 33 kDa were identified, none of which radiolabel with 3H-ethanolamine. While the 39-kDa polypeptide was Endo H resistant, the other isoforms were sensitive to Endo H digestion. Pulse chase experiments and molecular weights of the deglycosylated core polypeptides suggest a precursor to product relationship between the intracellular water-soluble species and the mature 39-kDa secreted Qa-2 molecule. This relationship is supported by the observation that murine L cells transfected with the Qa-2 encoding class I gene Q7 fail to express membrane-bound Qa-2 molecules yet synthesize both intracellular water-soluble and secreted Qa-2 molecules. These findings argue for a pathway in which secreted soluble Qa-2 molecules are derived from intracellular precursors.
Mol Immunol 1991 Nov
PMID:Biosynthesis of glycophospholipid bound and secreted murine class I Qa-2 polypeptides. 196 Dec 2

Further genetic evidence is provided here that Bradyrhizobium japonicum possesses a mitochondria-like electron-transport pathway: 2[H]----UQ----bc1----c----aa3----O2. Two Tn5-induced mutants, COX122 and COX132, having cytochrome c oxidase-negative phenotypes, were obtained and characterized. Mutant COX122 was defective in a novel gene, named cycM, which was responsible for the synthesis of a c-type cytochrome with an Mr of 20,000 (20K). This 20K cytochrome c appeared to catalyse electron transport from the cytochrome bc1 complex to the aa3-type terminal oxidase and, unlike mitochondrial cytochrome c, was membrane-bound in B. japonicum. The Tn5 insertion of mutant COX132 was localized in coxA, the structural gene for subunit I of cytochrome aa3. This finding also led to the cloning and sequencing of the corresponding wild-type coxA gene that encoded a 541-amino-acid protein with a predicted Mr of 59,247. The CoxA protein shared about 60% sequence identity with the cytochrome aa3 subunit I of mitochondria. The B. japonicum cycM and coxA mutants were able to fix nitrogen in symbiosis with soybean (Fix+). In contrast, mutants described previously which lacked the bc1 complex did not develop into endosymbiotic bacteroids and were thus Fix-. The data suggest that a symbiosis-specific respiratory chain exists in B. japonicum in which the electrons branch off at the bc1 complex.
Mol Microbiol 1990 Dec
PMID:Genetic analysis of the cytochrome c-aa3 branch of the Bradyrhizobium japonicum respiratory chain. 196 17

The emergence of Biotechnology has provided pharmacologists with a variety of methods for investigating the structure, the function, and the regulation of membrane-bound receptors with a precision that was not imagined even five years ago. These new tools have been developed and used to analyze the known catecholamine beta 1- and beta 2-adrenergic receptors and to discover and study a new subtype, the beta 3 receptor. We review here the salient features of each of these three receptors, compare their structural and functional properties, and propose models to explain their differential regulation in time and space. A whole family of proteins has now been found to share with the beta-adrenergic receptors their most prominent features, including seven transmembrane domains and coupling with GTP-binding "G" proteins. We therefore propose that the biotechnology-based procedures developed for the beta-adrenergic receptors will be well applicable to the other members of this "R7G" family of receptors.
Mol Neurobiol
PMID:Biotechnology of beta-adrenergic receptors. 196 19

Rat brain somatostatin (SRIF) receptors were solubilized in an active form with the detergent 3-[(cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). Solubilized SRIF receptors were detected with the stable SRIF analog 125I-MK 678. CHAPS solubilized approximately 30% of membrane-bound SRIF receptors. 125I-MK 678 binding to the solubilized SRIF receptors reached equilibrium by 90 min and dissociated from the receptor with a t1/2 of 60 min. The binding of 125I-MK 678 to the solubilized SRIF receptor was of high affinity and was selective. The characteristics of 125I-MK 678 binding to the solubilized and membrane-bound SRIF receptors were similar. The solubilized brain SRIF receptor specifically bound to a wheat germ agglutinin-Sepharose column, suggesting that it is a glycoprotein. Analysis of the solubilized SRIF receptor by gel exclusion chromatography on an AcA 34 Ultrogel column revealed that its molecular mass is approximately 400 kDa. This mass is probably representative of the receptor complexed with other proteins or molecules. Further characterization of the fractionated 400-kDa species by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting indicated that Gi and Go may be associated with the solubilized SRIF receptor. This is supported by the finding that guanosine-5'-O-(3-thio)triphosphate abolished 125I-MK 678 binding to the solubilized SRIF receptor. Antibodies directed against a synthetic peptide corresponding to a region of the C-terminal of Gia, which specifically immunoprecipitate Gia, immunoprecipitated over 24% of the solubilized SRIF receptor, suggesting that the receptor, in part, is coupled to Gi. These studies describe for the first time the characterization of the solubilized SRIF receptor in an active form. The ability to solubilize the SRIF receptor should allow for further characterization of its physical properties.
Mol Pharmacol 1990 May
PMID:Solubilization of active somatostatin receptors from rat brain. 197 Oct 88


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