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)

The enthalpy of helix-coil transition of DNA (delta H) is determined from the experiments on DNA melting with ligands by means of absolutely general formula, which contains only values directly known from the experiment (M.D. Frank-Kamenetskii, and A.T. Karapetian, Mol. Biol. USSR 6, 621 (1972)) with the combination of the "area" method (P.O. Vardevanian, et al., Biophysica 28, 130 (1983)). The experimentally obtained data show that delta H depends on both concentration of Na+ in solution and GC-content of DNA and is of high accuracy.
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PMID:Enthalpy of helix-coil transition of DNA: dependence on Na+ concentration and GC-content. 227 91

By the methods of heat denaturation and luminescence the interaction between an antitumor drug prospidine and DNA in aqueous solutions at two ionic strengths (0.1 and 0.001 M NaCl) and at various prospidine concentrations was studied. For the first time it has been demonstrated that the interaction occurs at 0.1 M NaCl and therapeutic prospidine concentrations. In the framework of Frank-Kamenetsky's theory of melting of a polymer with stabilizing ligands the size of the binding site and binding constants (K) with the decrease of ionic strength, the lack of alterations in the DNA UV absorption spectrum on complex formation and the data on the competitive binding of ethydium bromide suggest that at the first stage of the reaction an external complex is formed due to electrostatic interactions between quaternary nitrogen atoms of prospidine and DNA phosphate groups. Incubation of the complex at 37 0 C leads to a decrease of the DNA melting temperature and hyperchromic effect. Presumably this is due to the relatively slow formation of chemical bonds between alkylating groups of prospidine and nucleophilic groups of DNA bases, which results in the destabilization and denaturation of DNA. It is concluded that the interaction between prospidine and DNA must be taken into consideration when studying the molecular mechanism of prospidine antitumour activity.
Mol Biol (Mosk)
PMID:[Thermodynamic and spectral study of DNA-prospidin complex]. 260 45

Three-dimensional image reconstruction has been applied to electron micrographs of noncrystalline, negatively stained ribosomes obtained from Escherichia coli. Several independent reconstructions all show an overall appearance resembling models that had been derived earlier by direct visual interpretation of electron micrographs. The reconstructed ribosomes show numerous structural details not recognized previously, some of which may be functionally significant. A large elongate cavity (approximately 8-nm long x 5-nm wide x 6-nm [maximal] deep) is present on the surface of the ribosome near the base of its stalk and is identifiable as a portion of a feature termed the interface canyon, which was detected in prior reconstructions of the large ribosomal subunit (Radermacher, M., T. Wagenknecht, A. Verschoor, and J. Frank. 1987. EMBO (Eur. Mol. Biol. Organ.) J. 6:1107-1114). On the back of the ribosome, near the base of the central protuberance, is a hole leading to the interface canyon, which likely represents an exit site for the elongating polypeptide produced during protein biosynthesis. The exposed portion of the interface canyon appears well suited to bind two tRNA molecules in a configuration that is consistent with biochemical and structural data on the mechanism of peptide bond biosynthesis.
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PMID:Three-dimensional reconstruction of the ribosome from Escherichia coli. 264 63

Three to six mg of the millimolar Ca2+-requiring proteinase (m-calpain) were obtained from 1 kg bovine cardiac muscle (fresh wt) and some enzymatic properties of this proteinase were determined. Activity of bovine cardiac m-calpain decreases as ionic strength increases from 75 to 1000 mM. Maximal activation of m-calpain by Ca2+, La3+, Ba2+, and Mn2+ occurs at 2 to 3 mM concentrations of each of these divalent cations, but La3+ activation is only 20 to 25% and Ba2+ and Mn2+ activation only 6 to 10% as great as Ca2+ activation. Maximum Sr2+ activation occurs at 20 mM Sr2+ and is 90 to 95% of maximum Ca2+ activation. Mg2+, Zn2+, Cr2+, and Cd2+ do not activate m-calpain when added alone; Mg2+ does not affect, but Zn2+ inhibits, Ca2+-stimulated activity. The nonionic detergents, Triton X-100 and Brij 35, activate m-calpain 1.6- to 2.0-fold but do not change its Ca2+ requirement. Sodium dodecyl sulfate and urea inhibit m-calpain completely at 0.045% and 2.0 M, respectively. Because they bind Ca2+ needed for activation, ATP, ADP, and ITP inhibit m-calpain. The trypsin inhibitors, phenylmethylsulfonyl fluoride, ovomucoid trypsin inhibitor, ovoinhibitor, aprotinin, alpha 1-antiproteinase inhibitor, soybean trypsin inhibitor, and lima bean trypsin inhibitor do not affect m-calpain activity; m-calpain does not release measureable quantities of acid-soluble peptides from a rabbit skeletal sarcoplasmic protein fraction but does degrade rabbit skeletal myofibrils and casein.
J Mol Cell Cardiol 1988 Nov
PMID:Some properties of the millimolar Ca2+-dependent proteinase from bovine cardiac muscle. 285 32

The Ca2+/Mg2+ ATPase of the rat heart sarcolemmal particles was solubilized with Triton X-100 after treating the membranes with trypsin and purified by high speed centrifugation, ammonium sulfate fractionation, hydrophobic chromatography and gel filtration. The purified enzyme was seen as a single protein band in non-denaturing polyacrylamide gel electrophoresis and its molecular weight by gel filtration was found to be about 240,000. The enzyme utilized Ca-ATP or Mg-ATP as a substrate with high affinity sites (Km = 0.12-0.16 mM) and low affinity sites (Km = 1 mM). The enzyme also utilized CTP, GTP, ITP, UTP and ADP as substrates but at a lower rate in comparison to ATP. The enzyme was activated by Ca2+ (Ka = 0.4 mM) and Mg2+ (Ka = 0.2 mM) as well as by other cations in the order Ca2+ greater than Mg2+ greater than Mn2+ greater than Sr2+ greater than Ba2+ greater than Ni2+ greater than Cu2+. The ATPase activity in the presence of Ca2+ was markedly inhibited by Mg2+, Mn2+, Ni2+ and Cu2+ whereas the monovalent cations such as Na+ and K+ were without effect. The enzyme did not exhibit Ca2+ stimulated Mg2+ dependent ATPase activity and was insensitive to calmodulin, ouabain, verapamil, D-600, oligomycin, azide and vanadate. Optimum pH for Ca2+ or Mg2+ ATPase activity was 8.5-9.0. In view of the possible ectoenzyme nature of the ATPase, its role in adenine nucleotide and Ca2+ metabolism in the myocardium is discussed.
Mol Cell Biochem 1988 May
PMID:Purification and characterization of a Ca2+/Mg2+ ecto-ATPase from rat heart sarcolemma. 297 73

There is evidence that the steep ascending limb of the force-length curve in cardiac muscle (Frank-Starling relation) is based on a length-dependence of myofilament Ca2+ sensitivity. Previous work from this laboratory has indicated that in the sarcomere length range corresponding to the ascending limb of the cardiac force length curve (1.7 to 2.3 microns) the Ca2+-troponin C affinity is length-dependent. In this study Ca2+ binding to chemically skinned bovine cardiac muscle bundles was measured during ATP-induced force generation with fiber bundles having sarcomere lengths of 2.2 to 2.4 microns and 1.6 to 1.8 microns. A double isotope technique was used to make concurrent determinations of the force-pCa and bound Ca2+-pCa relationships. At the longer sarcomere lengths the fibers bound, at saturation, an amount of Ca2+ equivalent to approximately 3 mol Ca2+/mol troponin C. Force development appeared to be coupled to titration of the single, low-affinity Ca2+-specific site. In the pCa range 7.0 to 6.0 sarcomere length had no effect on Ca2+ binding. In the pCa range 6.0 to 5.0, in which force increased steeply, there was, in addition to a decreased relative force, a significant reduction in bound Ca2+ at the shorter sarcomere length. Thus sarcomere length appears to influence the Ca2+ binding properties of the regulatory site on troponin C. These data provide direct evidence that length-dependent modulation of Ca2+-troponin C affinity may make a major contribution to the force-length relationship in cardiac muscle.
J Mol Cell Cardiol 1988 Aug
PMID:Bound calcium and force development in skinned cardiac muscle bundles: effect of sarcomere length. 322 7

The pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) of Leishmania major promastigotes is a multimer of 59 kDa subunits having an Mr 181000. It is activated by its substrate phosphoenolpyruvate (PEP) in a positively cooperative manner, and heterotropically by fructose 1,6-bisphosphate (FBP). Kinetics with regard to the phosphate acceptor adenosine 5'-diphosphate (ADP), MgCl2, and KCl are hyperbolic and unaffected by FBP. The enzyme is strongly inhibited by the reaction product ATP, as well as GTP and ITP, and to a lesser degree by citrate. Of seven amino acids reported to inhibit the pyruvate kinases of other organisms, none have any effect on the L. major pyruvate kinase in vitro. The enzyme shows its maximum activity at pH 7.0 in the absence of FBP, and at pH 7.6 in its presence. Contrary to previous suggestions, the enzyme appears to be well-suited for a regulatory role in the metabolism of an aerobic organism capable of net glucose synthesis.
Mol Biochem Parasitol 1988 Jan 15
PMID:Purification and characterization of a metabolite-regulated pyruvate kinase from Leishmania major promastigotes. 334 4

Several guanine nucleotide analogs, in one series of which a hydrogen on the 2-amino group is replaced with the p-n-butylphenyl group (BuPGNP derivatives), were used to probe the GTP binding domain of bovine transducin. The order of apparent binding affinities in a series of nucleoside 5'-triphosphates was GTP gamma S greater than GTP approximately BuPGTP greater than dGTP approximately ITP much greater than ATP, values which were 30-100 times higher than affinities of the corresponding 5'-diphosphates. A derivative bearing a 6-aminohexylamino group on the gamma-phosphate, BuPGTP X C6, had a 60-fold lower affinity compared to BuPGTP. In contrast, the p-n-butylphenyl substituent on the 2-amino group had little effect on the binding affinity relative to GTP. Substitutions at the 2-amino group had little effect on either the hydrolysis of the derivatives by the GTPase activity associated with the alpha-subunit of transducin or the activation of cGMP phosphodesterase. The results indicate that the GTP binding domain of transducin is similar in tertiary structure to the corresponding domain of EF-Tu. The 5'-phosphates of GTP are oriented in the binding site of transducin so that the bulky C6 group of BuPGTP X C6 dramatically interferes with binding. The 2-amino group on the guanine ring is probably located at the periphery of the binding site, with the p-n-butylphenyl substituent of BuPGTP facing outward and only weakly interacting with the protein. BuPGTP should be an excellent parent compound for development of novel probes of G-protein interactions with other cellular proteins involved in receptor signal transduction.
Mol Pharmacol 1986 Dec
PMID:Ability of guanine nucleotide derivatives to bind and activate bovine transducin. 353 83

Isolated rat liver lysosomes were incubated with [14C]methemoglobin under various conditions. Optimal pH for the in vitro proteolysis was found to be 4-5. To evaluate whether or not degradation of added proteins could be due to enzyme leakage the integrity of the lysosomes was measured. Isolated lysosomes were found to be stable for up to 10 min of incubation at pH 5.5 and for 30 min at pH 7. The degradation of three different proteins (methemoglobin, ovalbumin, and lysozyme) was analyzed. No correlation was detected between rate of breakdown and physical properties of the proteins. Leupeptin, chloroquine, and propylamine inhibited proteolysis of added proteins by 45-65% in both neutral and acid milieu. Possible energy requirement was tested by the addition of Mg2+ and ATP to the incubation medium. A dose-dependent increase in proteolytic rate was found when ATP was added to the lysosomal suspension, a finding most likely due to acidification of the lysosomes and ensuing increased degradation. GTP and ITP were somewhat less effective. The noncleavable ATP analogue 5'-adenylylimidodiphosphate gave no stimulation. The ATP-driven proteolysis was inhibited by ethylmaleimide. Isolated lysosomes were also incubated with ferritin in order to visualize a possible uptake process of a protein in the electron microscope. Following incubation, ferritin particles were seen inside intralysosomal vesicles which appeared to be formed by invagination of the lysosomal membrane, a process designated microautophagy. The results thus support the notion that isolated lysosomes may micropinocytose and degrade exogenously added proteins and that this process is ATP dependent.
Exp Mol Pathol 1985 Feb
PMID:Uptake--microautophagy--and degradation of exogenous proteins by isolated rat liver lysosomes. Effects of pH, ATP, and inhibitors of proteolysis. 396 51

The Ca2+-dependent ATPase was solubilized from rat heart sarcolemmal membranes upon digestion with trypsin and was found to be different from Ca2+-stimulated Mg2+-dependent ATPase (Dhalla, N. S., Anand-Srivastava, M. B., Tuana, B. S., and Khandelwal, R. L. (1981) J. Mol. Cell. Cardiol. 13, 413-423). The enzyme was purified by high speed centrifugation, ammonium sulfate fractionation, and column chromatography and was seen as a single protein band in nondenaturing polyacrylamide gel electrophoresis. In sodium dodecyl sulfate-acrylamide gels, the enzyme dissociated into two subunits or fragments with molecular weights of about 55,000 and 12,000. The molecular weight of the enzyme, estimated by gel filtration on a Sephadex G-100 column, was found to be about 67,000. The enzyme utilized ATP with a Km of 0.20-0.26 mM but was also able to utilize ITP, CTP, GTP, and ADP as substrates at much lower rates. It was activated by Ca2+ with a Ka of 0.13-0.21 mM; it was also activated by other cations in the order Ca2+ greater than Mn2+ greater than Sr2+ greater than Ba2+ greater than Mg2+. Divalent cations like Cu2+, Ni2+, and Mg2+ were potent inhibitors. The enzyme was insensitive to ouabain, verapamil, oligomycin, cyanide, and vanadate but was markedly inhibited by N-ethylmaleimide. Calmodulin failed to stimulate Ca2+-dependent ATPase and instead inhibited slightly. Unlike K+, Na+ produced a marked inhibition of the Ca2+-dependent ATPase activity, and this inhibition was associated with an 8- 10-fold decrease in the affinity of the enzyme for Ca2+. The competitive action of Na+ indicates that the Ca2+-dependent ATPase may be a site of Na+-Ca2+ antagonism in the cell membrane.
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PMID:Purification and characterization of a Ca2+-dependent ATPase from rat heart sarcolemma. 621 55


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