Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of magnesium ions on the binding of the anticancer drug vinblastine to calf brain tubulin were investigated by a batch gel equilibration method. Magnesium ions at 1 mM strongly enhanced the binding of the first vinblastine molecule to each tubulin dimer without affecting either the drug affinity toward the rest of the binding site or the total stoichiometry of the vinblastine binding to tubulin. Sedimentation velocity studies indicated that magnesium ions can enhance strongly the vinblastine-induced tubulin self-association and suggested that the drug-induced self-association still proceeds through the isodesmic indefinite mechanism in the presence of the divalent cation. In PG buffer (0.01 M NaPi, 10(-4) M GTP, pH 7.0) containing more than 2.5 mM MgCl2, vinblastine induced tubulin to form large amorphous aggregates. The aggregate formation was rapid and took place at a drug stoichiometry between 0.7 and 1.0 mol of vinblastine per mole of tubulin dimers. Increasing the solution ionic strength decreased the rate of aggregate formation. Between an ionic strength of 0.05 and 0.1, the self-association led to the formation of paracrystalline aggregates instead of the amorphous ones. The results indicated that the binding of only the first vinblastine molecule to each tubulin dimer is linked to the self-association of the protein. They also confirmed our previously proposed rationale for the disagreement among the vinblastine-tubulin binding constants reported in the literature in terms of the different magnesium ion concentrations and ionic strength of the buffers used in the various studies.
 ...
PMID:Interaction of vinblastine with calf brain tubulin: effects of magnesium ions. 379 May 19

Effect of actinomycin D, an antibiotic, was investigated on the biological function of tubulin from bovine brain. The microtubule assembly was inhibited nearly completely when an equal molar ratio of actinomycin D and tubulin was used. The depolymerisation of the same, however, was not altered under the same conditions. The competence of tubulin to bind colchicine and GTP was also not affected. Chromatographic and the spectrophotometric studies showed that 0.94 mol of actinomycin D binds per mole of tubulin.
 ...
PMID:Inhibition of microtubule assembly by actinomycin D, an anti-tumour drug. 379 88

To determine whether tubulin polymerization requires the bivalent metal-GTP complex with the gamma-phosphate in the dianionic form, the effect of GTP(gamma F) on the polymerization process was studied, in the presence of either magnesium or manganese. P3-fluoro P1-5'-guanosine triphosphate (GTP(gamma F)) was a competitive inhibitor (Ki = 1.8 X 10(-4) M) of the GTPase activity of tubulin-colchicine complex, stopped the polymerization process during the course of reaction and no depolymerization occurred. This indicates that GTP(gamma F) has access only to the nucleotide exchangeable site of the free tubulin dimer. Tubulin has one mole of magnesium tightly bound per mole of dimer. In order to know whether the inhibitory effect of GTP(gamma F) was due to the release of the metal, magnesium was replaced for manganese (a paramagnetic ion) and the paramagnetic effect of manganese on the fluorine NMR signal from the GTP(gamma F)-tubulin-metal complex was followed. Longitudinal and transversal relaxation rates measurements of the 1 degree F-NMR signal allowed to determine that the upper distance from the manganese site to the fluorine atom was between 6 and 8 A. These studies demonstrate that the dianionic form of the terminal phosphate of the metal-GTP complex, at the nucleotide exchangeable site, is essential to stimulate tubulin polymerization.
 ...
PMID:Role of the dianionic form of the GTP gamma-phosphate in the polymerization process of tubulin. 391 58

The effect of rifampicin on the biological properties of bovine brain tubulin was investigated. Assembly of microtubules was almost completely blocked by rifampicin, whereas the depolymerization was not affected. The drug was found to inhibit both colchicine and GTP binding to tubulin. Association of rifampicin with tubulin was confirmed by spectrophotometric method. Binding of rifampicin was found to be dependent both on temperature and time. At 0 degrees for 1 hr 0.84 moles of rifampicin were bound per mole of tubulin.
 ...
PMID:Effect of rifampicin on the biological activity of tubulin. 405 91

Bacteriophage T3-induced RNA polymerase, upon copying its specific template, native T3 DNA, initiates RNA chains only with GTP. Denaturation of the DNA results in loss of template specificity for the polymerase. With denatured T3 DNA as template, T3 polymerase initiates RNA chains with both ATP and GTP, and the average length of the resulting RNA chains is markedly reduced. Studies of the polymerase reaction with native T3 DNA in vitro show that T3 polymerase is able to terminate RNA synthesis with the release of RNA chains from the template DNA. Polymerase is also released in the process and, acting catalytically, reinitiates new RNA chains. Many moles of RNA chains are thus formed per mole of polymerase added to the reaction mixture.
 ...
PMID:Initiation, release, and reinitiation of RNA chains by bacteriophage-T3-induced polymerase from T3 DNA templates (E. coli-guanosine triphosphate terminus-purified polymerase). 455 May 10

The Ca(++) transport mechanism in the red cell membrane was studied in resealed ghost cells. It was found that the red cell membrane can transport Ca(++) from inside the cell into the medium against great concentration gradient ratios. Tracing the movement of (45)Ca infused inside red cells indicated that over 95% of all Ca(++) in the cells was transported into media in 20 min incubation under the optimum experimental conditions. The influence of temperature on the rate constant of transport indicated an activation energy of 13,500 cal per mole. The optimum pH range of media for the transport was between 7.5 and 8.5. As energy sources, ATP(1), CTP, and UTP were about equally effective, GTP somewhat less effective, and ITP least effective among the nucleotides tested. The Ca(++) transport does not appear to involve exchange of Ca(++) with any monovalent or divalent cations. Also, it is not influenced by oligomycin, sodium azide, or ouabain in high concentrations, which inhibit the Ca(++) transport in mitochondria or in sarcoplasmic reticulum. In these respects, the Ca(++) transport mechanism in the red cell membrane is different from those of mitochondria and the sarcoplasmic reticulum.
 ...
PMID:Studies on the active transport of calcium in human red cells. 535 89

The subunit protein has been isolated from the central-pair and outer-doublet microtubules of sea urchin sperm tails. Both proteins have a sedimentation constant of 6S and a molecular weight of 120,000. Both are converted to a 60,000 molecular weight species by denaturation in 6 M guanidine hydrochloride and reduction with mercaptoethanol. The reduced-alkylated proteins have the same R(f) on disc electrophoresis, and the same amino acid composition, which is very similar to that of muscle actin. The central-pair protein has one binding site for colchicine per 120,000 g. Both proteins appear to have a guanine nucleotide binding site, but the ability to bind GTP in solution has been demonstrated only for the central-pair protein. Although 1 mole of guanine nucleotide is bound per 60,000 g to outer-doublet tubules, the protein obtained by dissolving the doublets at pH 10.5 has lost the guanine nucleotide-binding site and also shows little or no colchicine-binding activity. Comparison of the properties of the isolated protein with electron microscopic evidence on structure of microtubules suggests that the chemical subunit (M = 120,000) consists of two of the 40 A morphological subunits.
 ...
PMID:Properties of the protein subunit of central-pair and outer-doublet microtubules of sea urchin flagella. 566 6

Taxol induces the in vitro assembly of calcium stable microtubules from flagellar tubulin solubilized from sea urchin (Strongylocentrotus purpuratus) sperm tail outer doublets by sonication. Assembly occurs in the presence or absence of exogenous GTP. The drug (10 microM) reduces the critical concentration of protein required for assembly to less than or equal to 0.04 mg/ml. 3H-Taxol binds specifically to both isolated flagellar outer doublets and to reassembled microtubules with calculated maximal binding ratios of 0.25 and 1.32 moles taxol/mole polymerized flagellar tubulin dimer, respectively. We suggest that the discrepancy in maximal binding ratios may result from the presence of an endogenous molecule(s) along the surface of outer doublet microtubules that restricts taxol binding to that structure.
 ...
PMID:Taxol binds differentially to flagellar outer doublets and their reassembled microtubules. 613 33

The substrate specificity of diadenosine 5',5"'-P1,P4-tetraphosphate pyrophosphohydrolase from Physarum polycephalum for dinucleoside polyphosphates has been determined by high-performance liquid chromatography (HP-LC). Elution of a strong anion-exchange resin with a pH and ionic strength gradient of ammonium phosphate separates a series of monoadenosine and diadenosine polyphosphates. Most of the corresponding guanine nucleotides are also resolved on this HPLC system. One mole each of Ap4A and Gp4G is symmetrically hydrolyzed to 2 mol of ADP and GDP, respectively. Ap3A, Ap5A, Ap6A, and Ap4 are hydrolyzed, and in each case ADP is one of the products. Gp3G, Gp5G, Gp6G, and Gp4 are also substrates, and in each case GDP is one of the products. AMP, ADP, ATP, Ap2A, ADPR, GMP, GDP, GTP, NAD+, and NADP+ are not substrates. No hydrolysis of the cap dinucleotides m7Gp3Am and m7Gp3Cm was detected by HPLC. Diadenosine tetraphosphate pyrophosphohydrolase preparations were also assayed for adenylate kinase, nucleotide diphosphate kinase, NAD(P)+ pyrophosphohydrolase, phosphodiesterase, cyclic nucleotide phosphodiesterase, phosphatase, and ribonuclease activities. These enzymic activities were not detectable in diadenosine tetraphosphate pyrophosphohydrolase. The symmetrical hydrolysis of Ap4A and Gp4G is an unique catalytic property that distinguishes diadenosine tetraphosphate pyrophosphohydrolase from P. polycephalum from diadenosine tetraphosphate phosphohydrolases from other organisms.
 ...
PMID:Diadenosine 5',5"'-P1,P4-tetraphosphate pyrophosphohydrolase from Physarum polycephalum. Substrate specificity. 629 57

The characteristics of the binding of the dopamine receptor antagonist [3H]spiroperidol to rat striatal membranes were examined at six different incubation temperatures ranging from 1 degree to 37 degrees. Although the number of receptors labeled at each temperature was identical, the affinity of the receptor for [3H]spiroperidol decreased 10-fold as the incubation temperature was lowered from 37 degrees to 1 degree. The binding of [3H]spiroperidol was entropy-driven (delta S degree = +80 cal/mole-deg), endothermic (delta H degree = +10 kcal/mole), and exergonic (delta G degree = -13 kcal/mole). Qualitatively similar results were found for (+)-butaclamol, another dopamine receptor antagonist. The binding of the agonists dopamine and (+/-)-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene to sites labeled by [3H]spiroperidol in the striatum also appeared to be entropy-driven (delta S degree = +35 cal/mole-deg). In contrast to the results obtained in studies with antagonists, however, the affinity of the receptor for agonists was independent of the incubation temperature between 8 degrees and 37 degrees. Competition curves for the inhibition of [3H]spiroperidol binding by agonists became increasingly complex as the incubation temperature was lowered. The addition of GTP reduced the affinity of the receptor for agonists at all temperatures but did not simplify interpretation of these complex curves. At 1 degree there was a decrease in the affinity of the receptor for dopamine, and the effect of GTP was abolished.
 ...
PMID:Thermodynamic differences between agonist and antagonist interactions with binding sites for [3H]spiroperidol in rat striatum. 683 99


<< Previous 1 2 3 4 5 6 7 Next >>