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)

Binding of thyrotropin-releasing hormone (TRH, thyroliberin) to receptors in chilled membrane resuspensions from sheep anterior pituitary glands is reduced in affinity almost 2-fold by micromolar concentrations of guanosine 5'-triphosphate (GTP) and the hydrolysis-resistant analog guanyl-5'-yl imidodiphosphate (GppNHp) added to tissue during a 10-min preincubation at 37 degree C. Guanosine 5'-diphosphate (GDP) produced a similar effect at 1 mM, while GMP, ATP, ADP and AMP appeared relatively inactive. The number of TRH-binding sites was not affected by the nucleotide treatments. These results are consistent with reports of guanine nucleotide effects on other receptor types and with evidence suggesting an adenylate cyclase mechanism for some of TRH's effects in the anterior pituitary.
Mol Cell Endocrinol 1981 Jan
PMID:Guanine nucleotides modulate TRH-receptor binding in sheep anterior pituitary. 625 3

Guanylyltransferase, an enzyme that catalyzes formation of mRNA 5'-terminal caps, was isolated from HeLa cell nuclei. The partially purified preparation, after incubation with [alpha-32P]GTP, yielded a single radiolabeled polypeptide by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The guanylylated product was stable at neutral and alkaline pHs and had a pI of 4 by isoelectric focusing. An apparent molecular weight of approximately 68,000 was estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. The formation of a covalently linked, radiolabeled GMP-protein complex and the associated release of PPi required the presence of [alpha-32P]GTP and divalent cations and incubation between pH 7 and 9. Reaction with [beta-32P]GTP, [alpha-32P]CTP, [alpha-32P]UTP, or [alpha-32P]ATP did not label the approximately 68,000-dalton polypeptide. Phosphoamide linkage of the GMP-enzyme complex was indicated by its sensitivity to cleavage by acidic hydroxylamine or HCl and not by NaOH or alkaline phosphatase. Both formation of the GMP-enzyme intermediate and synthesis of cap structures of type GpppApG from GTP and ppApG were remarkably temperature independent; the rates of enzyme activity at 0 to 4 degrees C were 30% or more of those obtained at 37 degrees C. Radiolabeled GMP-enzyme complex, isolated by heparin-Sepharose chromatography from reaction mixtures, functioned effectively as a GMP donor for cap synthesis with 5'-diphosphorylated oligo- and polynucleotide acceptors. Alternatively, protein-bound GMP could be transferred to PPi to form GTP. The formation of a guanylylated enzyme intermediate appears to be characteristic of viral and cellular guanylyltransferases that modify eucaryotic mRNA 5' termini.
Mol Cell Biol 1982 Aug
PMID:Covalent guanylyl intermediate formed by HeLa cell mRNA capping enzyme. 629 Aug 77

Angiotensin II binding sites in a rabbit ventricular myocardial particulate fraction were identified and characterized with the radioligand 125I-angiotensin II. The order of potency in competing with 125I-angiotensin II for these sites was similar to that observed in physiological studies. Computer-assisted analysis of the competition of binding sites for 0.3 nM 125I-angiotensin II by unlabeled angiotensin II (3 X 10(-11) M to 1 X 10(-5) M) demonstrated that optimal fitting of the competition curves was attained with a two-site model having one site of high affinity (KA1 = 2.4 +/- 0.6 X 10(9) M-1), low capacity (N1 = 7.8 +/- 0.8 fmoles/mg of protein) and a second site low affinity (KA2 = 9.6 +/- 0.6 X 10(6) M-1) and high capacity (N2 = 219 +/- 128 fmoles/mg of protein). Analysis of competition by Sar1-Ile8 angiotensin II for 125I-angiotensin II binding sites indicated that the antagonist interacted with the first site with high affinity (KA1 = 8 X 10(9) M-1), but interacted minimally with the second site (KA2 = 10(5) M-1). Monovalent cations (Na+, K+, Li+, NH4+) were roughly equipotent in decreasing 125I-angiotensin II binding by reducing the number of high-affinity sites (N1 = 2.6 +/- 0.7 fmoles/mg of protein with 100 mM Na+) without changing the affinity of either site or the number of low-affinity sites. The number of high-affinity sites was increased to 14.4 +/- 1.5 fmoles/mg of protein by 5 mM Mg2+. In the presence of divalent cations, nucleotides reduced binding of 125I-angiotensin II with the potency order guanosyl-5'-yl-imidodiphosphate greater than GTP greater than GDP greater than ATP greater than GMP. Guanosyl-5'yl-imidodiphosphate significantly reduced the affinity of the high-affinity site (KA1 = 1.0 +/- 0.2 X 10(9) M-1) and perhaps of the low-affinity site (KA2 = 1.0 +/- 2.2 X 10(6) M-1). Computer-assisted assessment of dissociation of 0.3 nM 125I-angiotensin II from rabbit myocardial membranes corroborated the equilibrium data: dissociation was biphasic (K-1 = 0.19 +/- 0.2 min-1 for a rapidly dissociating site, k-1 = 2.5 +/- 2.1 X 10(-3) min-1 for a slowly dissociating site); 5 mM Mg2+ did not significantly change either dissociation rate; but guanosyl-5'-yl-imidodiphosphate significantly increased dissociation rates from both sites. Despite the indirect evidence that these angiotensin II receptors interact with guanine nucleotide regulatory proteins, angiotensin II (10(-6) M) failed to influence adenylate cyclase activity. The physiological implications of the presence in ventricular myocardium of two distinct angiotensin II receptors and in particular the implications of a receptor-associated guanine nucleotide regulatory protein which does not couple to adenylate cyclase require further investigation.
Mol Pharmacol 1983 Sep
PMID:Characterization of the rabbit ventricular myocardial receptor for angiotensin II. Evidence for two sites of different affinities and specificities. 631 Mar 63

The modified purine nucleotide 8-oxo-guanosine-2'-phosphate binds at the pyrimidine binding site of ribonuclease-A. The O8-2'GMP inhibitor is in a syn conformation, with an intramolecular hydrogen bond between the N-3 atom of the base and the O-5' atom of the ribose. The essential groups of the protein involved in base recognition are O gamma 45 and N-45, which form hydrogen bonds to the five-membered ring of the heterocyclic base. Mobility of enzyme side-chains (viz. Lys41, Lys66, His119) close to the catalytic cleft of the protein allows conformational flexibility in the substrate binding region of ribonuclease-A. Inhibitor binding alters the solvent structure of the protein but the overall shape of the enzyme is not effected.
J Mol Biol 1983 Sep 25
PMID:Specificity of pancreatic ribonuclease-A. An X-ray study of a protein-nucleotide complex. 631 34

The in vivo regulation of ovarian gonadotropin and prolactin receptors and adenylate cyclase activity by FSH, and the potent GnRH agonist [D-Ala6]des-Gly10-GnRH N-ethylamide (GnRHa), was studied in immature hypophysectomized diethylstilbestrol-implanted rats. During FSH treatment over a 48 h period, FSH receptors increased 2-fold with the maximum response during the first 12 h, whereas LH and prolactin receptors increased by 10-fold and 6-fold with the maximum response from 12 to 48 h. Administration of GnRHa at any time during the 48 h period of FSH treatment inhibited the subsequent development of gonadotropin and PRL receptors. In contrast, administration of a single dose of 10 micrograms GnRHa after 48 h of FSH treatment stimulated follicular luteinization and caused increases in basal adenylate cyclase activity, ovarian weight and PRL receptor content, and concomitant decreases in gonadotropin receptors and adenylate cyclase responses. In the immature follicles of animals not primed with FSH, GnRHa caused progressive inhibition of FSH-sensitive adenylate cyclase activity, with a decrease in FSH receptors, but increased both basal and GMP-P(NH)P-stimulated adenylate cyclase activities. These results demonstrate that GnRHa causes marked inhibition of gonadotropin receptor expression in the basal and FSH-stimulated ovary. This decrease in gonadotropin receptors is an important component of the mechanism by which GnRH agonists inhibit ovarian gonadotropin-sensitive adenylate cyclase activity. In addition, these peptides exert stimulatory effects upon ovarian weight and basal adenylate cyclase activity, and cause an increase in PRL receptors and luteinization of mature ovarian follicles.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1984 Apr
PMID:GnRH agonist-induced inhibitory and stimulatory effects during ovarian follicular maturation. 632 79

Effects of dietary Streptococcus faecalis (SF) on aging were evaluated using 1-week, 6-month, and 27-month-old Wistar and SHR rats. SF was lyophilized and added to commercial pellets at 1%. SF inhibited hypertension in aging SHR. SF inhibited aging-related changes in a wide variety of tissues. These changes were a disarray of hepatic cords, portal fibrosis; calcification of cartilage matrix, dominance of chondroitin sulfate B, and keratosulfate over chondroitin sulfates A and C; aortic endothelial damage, segmental thickening, calcification, and chondroid cells in the intima; atrophy of epidermis and appendages, and increase in amorphous dermal matrix; waxy degeneration and atrophy of psoas muscles; increase in lipoperoxides in the serum, liver, and brain; and reduction of cyclic AMP and GMP in the serum. Histological changes of the xyphoid cartilage, aorta, mesenteric artery, liver, dorsal skin, and psoas muscles in 27-month-old SF rats were much less severe than those in controls.
Exp Mol Pathol 1983 Jun
PMID:Inhibition of aging changes by lyophilized Streptococcus faecalis in diet. 640 63

Purine metabolism in developing Schistosoma mansoni schistosomules was investigated in erythrocyte-free and serum-free media to eliminate possible contamination from host metabolites or enzymes. The absence of de novo purine nucleotide synthesis in the parasite was confirmed by the lack of incorporation of radiolabeled glycine or formate into the nucleotide pool. Adenosine and adenine were equally incorporated into adenine nucleotides. The incorporation was not affected by hadacidin, an inhibitor of succinyl AMP synthetase. Adenosine and adenine therefore appear to be converted to AMP without forming IMP as an intermediate. Guanosine was first converted to guanine which was then incorporated into guanine nucleotides. There was no appreciable interconversion between adenine nucleotides and guanine nucleotides. Hypoxanthine was incorporated into all purine nucleotides, but most of it (90%) was found in the adenine nucleotides. The equilibrium however, was shifted by hadacidin in favor of guanine nucleotides; an indication that hypoxanthine was converted first to IMP and then to AMP or GMP. These findings, together with the previous observation that S. mansoni lacks functional purine nucleoside kinases lead to the conclusion that all purine nucleosides are primarily converted to the corresponding purine bases. The latter are then incorporated into the nucleotide pool via individual purine phosphoribosyl transferases. The three enzymic activities for salvaging adenine, guanine, and hypoxanthine thus constitute the major network for purine salvage in S. mansoni schistosomules.
Mol Biochem Parasitol 1984 Apr
PMID:Purine salvage in Schistosoma mansoni schistosomules. 643 Dec 83

The anaerobic protozoon Tritrichomonas foetus was found incapable of de novo purine synthesis by its failure to incorporate radiolabeled glycine or formate into the nucleotide pool. It had, on the other hand, high activities in incorporating adenine, hypoxanthine or inosine. Radiolabel pulse-chase experiments indicated that adenine, hypoxanthine and inosine all entered the pool through conversion to IMP. The parasite contained hypoxanthine phosphoribosyl transferase, adenine deaminase and inosine phosphorylase, but no adenine phosphoribosyl transferase, inosine kinase or inosine phosphotransferase activity. Adenine and inosine had to be converted to hypoxanthine before incorporation. Adenosine was also rapidly converted to hypoxanthine in T. foetus cell-free extracts, but the presence of adenosine kinase in the parasite allowed some conversion of adenosine directly to AMP. Guanine and xanthine were directly incorporated into GMP and XMP, probably due to the guanine and xanthine phosphoribosyl transferase. There were also strong enzyme activities which convert guanosine to guanine and guanine to xanthine. A guanosine phosphotransferase was found in the 10(5) X g sedimentable fraction of T. foetus, and was capable of converting some guanosine to GMP. This network of T. foetus purine salvage suggests the importance of hypoxanthine-guanine-xanthine phosphoribosyl transferase activities in the parasite.
Mol Biochem Parasitol 1983 Aug
PMID:Purine salvage by Tritrichomonas foetus. 663 66

Cytosolic factors in a 50--75% (NH4)2SO4 fraction of the 105 000 x g supernatant of the renal cortex modulated adenylate cyclase activity in membrane preparations enriched in renal tubular cell basal--lateral membranes. The crude factor preparation had no effect on basal activity but it contained components that augmented the stimulated of the enzyme by NaF, parathyroid hormone (PTH), prostaglandin E1 (PGE1), and inhibited the activation of the enzyme by GMP--PNP. The factor(s) potentiating the stimulation by the hormones was partially purified (13-fold) by DEAE-cellulose and Sephadex G-75 chromatography. During purification, the component(s) that increased hormone-stimulated adenylate cyclase was separated from those affecting the activity in the presence of NaF and GMP--PNP. The factor(s) enhanced the PTH- and PGE1-stimulated enzyme at all concentrations of hormone, suggesting that the affinity for the hormone was not affected. The factor(s) was heat-stable. Partial proteolysis with chymotrypsin greatly reduced the ability of the factor(s) to enhance hormonal responsive adenylate cyclase. However, the factor(s) was resistant to trypsin digestion. The effect of the factor was not due to GTP, nor was GTP necessary for its action. Ca2+ was not needed for the enhancing activity of the factor(s). These findings suggest the presence in the cytosol of the kidney cortex of a protein(s) that regulates the response of renal adenylate cyclase to hormones. The relationship between this kidney cytosolic factor and those reported in other tissues remains to be established.
Mol Cell Endocrinol 1981 Mar
PMID:Regulation of hormone(PTH and PGE1)-stimulated adenylate cyclase by renal cytosolic factors. 721 2

The pathways of purine ribonucleotide synthesis and interconversion that are operative in the intact adult pig lung worm Metastrongylus apri were identified by radioisotope tracing. The rate of [14C]glycine incorporation into purines was low but sufficient to demonstrate synthesis de novo. Radioactively labelled adenine, hypoxanthine and guanine were readily taken up and converted to the corresponding mononucleotides. Most of the AMP and GMP formed were phosphorylated to the triphosphates. These two nucleotides were interconvertable by pathways in which IMP is an intermediate. Adenosine was converted to nucleotides by direct phosphorylation as well as via formation of hypoxanthine. The rate of synthesis of adenine nucleotides from hypoxanthine was 5-7 times that of guanine nucleotides; conversion of IMP to AMP and to xanthosine 5'-monophosphate were the rate-limiting steps.
Mol Biochem Parasitol 1981 Apr
PMID:Pathways of purine ribonucleotide biosynthesis in the adult worm Metastrongylus apri (Nematoda: Metastrongyloidea) from pig lung. 724 68


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