Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine triphosphatase from the thermophilic bacterium PS3(TF1) has been studied by solution X-ray scattering. A structural change in TF1 caused by the binding of ADP was observed by examining the difference between the radii of gyration of the unligated and ligated forms. The radius of gyration of the unligated TF1 was found to be 49.5 +/- 0.3 A, and it decreased by approximately 3% after ligation with ADP. The positions and the amplitudes of a subsidiary maximum and a shoulder in the scattering profile showed subtle change on nucleotide binding. The lower limit of the maximum length of TF1 was determined to be 165 A for the unligated form and 150 A for the ligated form. The shape analysis of TF1 was performed by model calculations for simple triaxial bodies or their complexes. Among the various models tested, the one that gave the best fit with the experimental data consisted of seven ellipsoids of revolution; six identical ellipsoids with semi-axes: a = b = 18.5 A and c = 74 A. arranged hexagonally, and the other with a = b = 28 A and c = 45 A, located below the other six on the 6-fold axis. On the basis of this model it was suggested that there is a structural change on ligation with nucleotides, consisting of a shrinkage of the six long ellipsoids by 6% along their major axes.
J Mol Biol 1983 Oct 15
PMID:Small-angle X-ray scattering study of adenosine triphosphatase from thermophilic bacterium PS3. 613 39

Three mutants producing thermosensitive DNA-dependent Adenosine triphosphatase (ATPase) I were screened from a collection of temperature-sensitive mutants of Escherichia coli K12. ATPase I purified to near homogeneity from one of the mutants (JE11000) possesses both thermosensitive DNA-dependent ATPase and DNA helicase activities. We have shown that ATPase I is encoded by the uvrD gene as first suggested by Oeda et al. (1982): (i) the thermosensitive ATPase I mutation present in JE11040 lies in or very close to the uvrD gene, (ii) ATPase I activity is absent in uvrD210, uvrD156, and uvrD252 mutants. Thus the thermosensitive mutations correspond to new uvrD mutations. However, the mutation present in JE11040 confers neither UV sensitivity nor mutator phenotype at high temperature. Evidence is presented that the mutant ATPase I is stabilized in vivo at 42 degrees C.
Mol Gen Genet 1983
PMID:Escherichia coli uvrD mutants with thermosensitive DNA-dependent adenosine triphosphatase I (helicase II). 614 Jun 19

Adenosine causes negative chronotropic and inotropic effects on cardiac tissue. We have investigated the nature of the cardiac adenosine receptor and its effector mechanisms in preparations of newborn chick heart. The adenosine analog [3H]N6 (L-phenylisopropyl) adenosine (L-PIA), an agonist at R-type adenosine receptors, bound with high affinity to receptors in crude and highly-purified membrane preparations. The KD was 3-5 nM. The receptor density was low in crude membranes (10 fmol/mg protein) but significantly enriched in purified sarcolemma (164 fmol/mg protein). Competition studies showed that N-ethylcarboxamide adenosine and N6(D-phenylisopropyl)adenosine were less potent than N6(L-phenylisopropyl)adenosine at the chick heart adenosine receptor, as expected for an Ri-type adenosine receptor. Gpp(NH)p decreased the binding of [3H]N6(L-phenylisopropyl)adenosine to chick heart membranes, suggesting that the guanine nucleotide converted the receptor to a lower affinity state. N6(L-phenylisopropyl)adenosine inhibited beta-adrenergic receptor stimulated adenylate cyclase activity. The IC50 for cyclase attenuation by N6(L-phenylisopropyl)adenosine was 1 microM. N6(L-phenylisopropyl)adenosine reversed the effect of the beta-receptor agonist isoproterenol on phospholamban phosphorylation in 32P-labelled slices of newborn chick hearts. This effect of N6(L-phenylisopropyl)adenosine was evident by 2 min, had an IC50 of 200 nM, and was prevented by the adenosine receptor antagonist 8-phenyltheophylline. Taken together, the results suggest that the antiadrenergic effects of adenosine on cardiac tissue are mediated by a decrease in membrane protein phosphorylation signalled by activation of Ri-adenosine receptors. The coupling mechanism between receptor activation and protein phosphorylation may be an attenuation of adenylate cyclase.
J Mol Cell Cardiol 1984 Oct
PMID:Inhibitory adenosine receptors in the heart: characterization by ligand binding studies and effects on beta-adrenergic receptor stimulated adenylate cyclase and membrane protein phosphorylation. 615 Oct 2

Adenosine, TMP, ADP, ATP and UpA along with guanosine and tis analogous derivatives have different reactivity towards [alpha-32P]UTP in abortive initiation reactions catalyzed by E. coli RNA polymerase on T2 DNA in the presence of Mg2+ or Mn2+. Rifampicin moderately inhibited almost all of the above mentioned reactions, except the ATP and the GTP which were even 2.5 times more reactive in the presence of this antibiotic.
Mol Biol (Mosk)
PMID:[Participation of various adenosine and guanosine derivatives in the abortive RNA synthesis initiation reaction: effect of Mg2+, Mn2+, and rifampicin]. 616 Mar 85

Genetic dissection of nucleoside transport in Leishmania donovani indicates that the insect vector form of these parasites possesses two biochemically distinct nucleoside transport systems. The first transports inosine, guanosine, and formycin B, and the second transports pyrimidine nucleosides and the adenosine analogs, formycin A and tubercidin. Adenosine is transported by both systems. A mutant, FBD5, isolated by virtue of its resistance to growth inhibition by 5 microM formycin B, cannot efficiently transport inosine, guanosine, or formycin B. This cell line is also cross-resistant to growth inhibition by a spectrum of cytotoxic analogs of inosine and guanosine. A second parasite mutant, TUBA5, isolated for its resistance to 20 microM tubercidin, cannot take up from the culture medium radiolabeled tubercidin, formycin A, uridine, cytidine, or thymidine. Both the FBD5 and the TUBA5 cell lines have about a 50% reduced capacity to take up adenosine, indicating that adenosine is transported by both systems. A tubercidin-resistant clonal derivative of FBD5, FBD5-TUB, has acquired the combined biochemical phenotype of each single mutant. The wild-type and mutant cell lines transport purine bases and uracil with equal efficiency. Mutational analysis of the relative growth sensitivities to cytotoxic nucleoside analogs and the selective capacities to take up exogenous radiolabeled nucleosides from the culture medium have enabled us to define genetically the multiplicity and substrate specificities of the nucleoside transport systems in L. donovani promastigotes.
Mol Cell Biol 1984 Jun
PMID:Genetic analysis of nucleoside transport in Leishmania donovani. 623 54

Crystalline complexes of tyrosyl-tRNA synthetase from Bacillus stearothermophilus were prepared with adenosine, AMP, ATP and PPi, all in the presence of tyrosinol, which binds strongly to the tyrosine binding site but cannot be adenylated by ATP. The hydrolysis of ATP in the presence of crystalline tyrosyl-tRNA synthetase (or redissolved crystals) was checked in the absence of tyrosine or with tyrosinol. No ATPase activity due to the enzyme was detected under these conditions. Difference Fourier analysis shows that tyrosinol binds to the tyrosine binding site with the same occupancy as the amino acid. Comparison between tyrosine and tyrosinol shows the location of the extra oxygen atom of the tyrosine carboxylate. Adenosine, AMP and ATP are weakly bound to the enzyme in the presence of tyrosinol. Even when ATP is present at a concentration greater than Km for adenylation, it is not sufficiently strongly bound to give a recognizable density for adenine. However, some significant peaks of density are present near the tyrosine binding site. One of them is at the usual ribose binding site, and may possibly represent ribose binding with a low occupancy. When AMP is bound a similar but not identical arrangement of density is observed.
J Mol Biol 1984 Mar 15
PMID:Interaction of crystalline tyrosyl-tRNA synthetase with adenosine, adenosine monophosphate, adenosine triphosphate and pyrophosphate in the presence of tyrosinol. 632 20

Adenosine diphosphate (ADP) is known to induce platelet shape change, aggregation and fibrinogen binding, followed by secretion. These processes are mediated by the binding of ADP to an externally oriented protein of the platelet plasma membrane. An affinity analog of ATP, a competitive inhibitor of the action of ADP, has been utilized to probe the structure and function of this receptor. FSBA (5'-p-fluorosulfonylbenzoyl adenosine) covalently modifies a single protein in intact platelets with Mr = 100 000 and concomitantly inhibits platelet shape change, aggregation and fibrinogen binding. Studies on platelet membranes demonstrate non-covalent association of ADP-binding protein with actin which is also labeled by FSBA but only in isolated membranes. This finding suggests a structural and functional coupling of the receptor to the contractile process. The putative ADP receptor covalently modified with FSBA is cleaved by chymotrypsin, a process that reverses the inability of the platelets to bind fibrinogen. Thus, the Mr = 100 000 polypeptide may be involved in the proteolytic exposure of fibrinogen binding sites on the platelet surface. The ability of FSBA to inhibit platelet aggregation and fibrinogen binding by prostaglandin H2 derivatives and epinephrine suggest that ADP is involved in these processes. However, the interaction is not at the receptor level since shape change, stimulated by PGH2 derivatives and yohimbine (epinephrine antagonist) binding are unaffected by FSBA. Finally, the action of ADP to inhibit PGE1- or PGI2-stimulated adenylate cyclase appears to be mediated by a receptor distinct for the protein modified by FSBA.
Mol Cell Biochem 1984
PMID:Characteristics of an ADP receptor mediating platelet activation. 632 60

Modification of phenylalanyl-tRNA synthetase from E. coli MRE600 by adenosine-5'-trimetaphosphate, phosphorylating analog of ATP was shown to bring about the enzyme inactivation in the reactions of tRNA aminoacylation and ATP-[32P]pyrophosphate exchange. ATP when added in the reaction mixture protects the enzyme against inactivation in both reactions and decreases the level of covalent attachment of the analog. Phenylalanine has no protective effect. tRNA exhibits slight protective effect. Adenosine-5'-trimetaphosphate modifies both types (alpha and beta) of subunits of phenylalanyl-tRNA synthetase which is of alpha 2 beta 2 structure. ATP protects both types of the enzyme subunits against the covalent attachment of the analog. Disposition of the ATP-binding centers in the contact region of the nonequivalent subunits of the enzyme was proposed. The level of covalent attachment of the analog to the enzyme exceeds the number of the enzyme active sites that may be a consequence of the other nucleotide-binding center labeling.
Mol Biol (Mosk)
PMID:[Modification of phenylalanyl-tRNA-synthetase from Escherichia coli MRE600 by adenosine-5'-trimetaphosphate]. 636 20

epsilon ATP is a substrate of phenylalanyl-tRNA synthetase and epsilon Ado is a competitive inhibitor of ATP in the reaction of tRNA aminoacylation (Ki = 1.6 mM). The association of phenylalanyl-tRNA synthetase with ATP or Ado results in synergistic binding of phenylalaninol and phenylalanine, respectively. However neither epsilon ATP nor epsilon Ado exhibit synergism. Adenosine- and ethenoadenosine-5'-trimethaphosphates are shown to be similar affinity reagents of phenylalanyl-tRNA synthetase. ATP being covalently bound to the enzyme shows essentially lower synergistic effect in comparison with free ATP. epsilon ATP-label is practically insensitive to the ligands namely ATP, Phe, phenylalaninol and is highly accessible for I- ions. The scheme of behaviour of affinity labels is assumed to be as follows: a) the formation of specific reagent-enzyme complex, b) the covalent attachment of the reagent to the enzyme, c) the covalent binding induced disruption of the specific complex formed before.
Mol Biol (Mosk)
PMID:[Adenosine- and ethenoadenosine-5'-trimetaphosphates: the effect of covalent bond formation on the state of the affinity label in the complex with phenylalanyl-tRNA-synthetase]. 639 Jan 77

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


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