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Query: UNIPROT:P06889 (Mol)
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Rate constants of 8-oxy-dGMP (8-hydroxy-dGMP) formation upon incubating dGMP in H2O solutions at different temperatures were determined with differential UV-spectroscopy. Extrapolation of rate constant values obtained at elevated temperatures to 37 degrees C gives k = 5.8 x 10(-10) s-1.M-1. The activation energy for the process was estimated to be 24 kcal/mole. In D2O solutions essential lowering of the activation energy (13 kcal/mole) and rising of rate constant (k = 3.7 x 10(-9) s-1.M-1 at 37 degrees C) were observed. The strong influence of D2O on the process points to the possible participation of singlet oxygen in a heat-induced formation of 8-oxy-dGMP. The obtained values of rate constants and activation energy induced by heat show that of all types of DNA damages currently known such as single strand scission, depurination, cytosine deamination and oxidation of guanyl residues to the 8-oxo-derivatives- the last process seems to be the strongest damage of DNA resulting in such biological consequences as mutagenesis, carcinogenesis and aging.
Mol Biol (Mosk)
PMID:[Kinetics of formation of 8-oxy-2'-deoxyguanosine-5'-monophosphate under the effect of heat: determination of rate constants and activation energy]. 133 39

We have examined the effect of 1-palmitoyl-2-(10-pyrenyl)decanoyl-sn-glycerol-3-phosphatidylcholine (Pyr-PC) concentration on the ratio of excimer fluorescence to monomer fluorescence (E/M) in L-alpha-dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles at 30 degrees C, with special attention focussed on the smoothness of the curve. We observed a series of dips, in addition to kinks, in the plot of E/M versus the mole fraction of Pyr-PC (XPyrPC). The observation of dips is a new finding, perhaps unique for Pyr-PC in DMPC since only kinks were observed for Pyr-PC in L-alpha-dipalmitoylphosphatidylcholine (DPPC) and in egg yolk phosphatidylcholine (egg-PC) (Somerharju et al., 1985. Biochemistry. 24: 2773-2781). The dips/kinks observed here are distributed according to a well defined pattern reflecting a lateral order in the membrane, and distributed symmetrically with respect to 50 mol% Pyr-PC. Some of the dips appear at specific concentrations (YPyrPC) according to the hexagonal super-lattice model proposed by Virtanen et al. (1988. J. Mol. Electr. 4: 233-236). However, the observations of dips at XPyrPC > 66.7 mol% and the kink at 33.3 mol% cannot be interpreted by the model of Virtanen et al. (1988). These surprising results can be understood by virtue of an extended hexagonal super-lattice model, in which we have proposed that if the pyrene-containing acyl chains are regularly distributed as a hexagonal super-lattice in the DMPC matrix at a specific concentration YPyrPC, then the acyl chains of DMPC can form a regularly distributed hexagonal super-lattice in the membrane at a critical concentration (1-YPyrPC). The excellent agreement between the calculated and the observed dip/kink positions, except for the dip at 74 mol% and the kink at 40 mol%, provides most compelling evidence that lipids are regularly distributed into hexagonal super-lattices in Pyr-PC/DMPC mixtures at specific concentrations. The physical nature of the dips not only gives us a better understanding of lipid lateral organization in membranes but also will lead to new theoretical considerations and experimental designs for exploring the relationship between lipid regular distribution and membrane functions.
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PMID:E/M dips. Evidence for lipids regularly distributed into hexagonal super-lattices in pyrene-PC/DMPC binary mixtures at specific concentrations. 142 Sep 34

X-ray small-angle diffraction, differential scanning calorimetry (DSC), and temperature scanning densitometry (TSD) were used to study the effect of delta-lysin on the phase transitions of lipid assemblies from 1,2-0-dixehadecyl-sn-glycero-3-phosphocholine (DHPC). The experiments were carried out in excess of water in a temperature range of 0-55 degrees C, and at low peptide concentrations between 10(-4) and 10(-2) moles peptide per mole phospholipid. The incorporation of delta-lysin into lipid assemblies alters the lipid structure without significant changes on the temperatures of phase transition from gel to liquid crystalline phase. The temperature of the main transition was nearly unaffected. A reduction in the transition volume of the lipids with increasing concentrations of delta-lysin was observed. The minor changes in these parameters were interpreted as long-range structural changes caused by the peptide incorporation. The results are discussed in terms of the concept of cooperative phase transition of entire clusters occurring within a membrane implying that relative stable domains of gel phase, and liquid crystalline phase co-exist.
Mol Biol Rep 1992 Sep
PMID:Effect of delta-lysin on the phase transitions of lipid assemblies. 145 57

In the mole crab Emerita asiatica, the main yolk proteins consist of two slow moving lipovitellins (Lv I and Lv II) of glycolipoprotein nature. Lv I cleaves into subunits (MW: 109,000 and 105,000) and Lv II gives rise to six subunits (MW: 65,000, 54,000, 50,000, 47,000, 44,000, and 42,000) in SDS-PAGE (with beta-mercaptoethanol). In order to observe the stability of Lv II as well as to achieve better resolution of the proteins, two different buffer systems (Phosphate buffered saline and tris-buffered saline), 40% sucrose, and glass distilled water were used as homogenizing media. Among them, better resolution was achieved with tris-buffered saline and 40% sucrose, and tris-buffered saline seems to be the ideal medium for elution of Lv II. The analysis of biochemical constituents of the major Lv II reveals a percentage composition of 69.325, 27.927, and 2.753 respectively for protein, lipid, and bound sugars. In the I stage embryo, protein comprises about 67.276%, lipid 29.65%, and bound sugars 3.015%. Vitellogenin (Vg) electrophoretically corresponding to the Lv I and Lv II was present in the female haemolymph during the entire period of embryogenesis. The number of subunits (8) of Vg in all stages remained unaltered and their approximate molecular weights were Vg1, 91,000; Vg2, 87,000; Vg3, 83,000; Vg4, 61,000; Vg5, 58,000; Vg6, 45,000; Vg7, 42,000; and Vg8, 38,000. Different proteins present in the embryos (I and IV stage) and the serum obtained from the animal carrying the I stage embryo were separated by gel-filtration in high performance liquid chromatography (HPLC). Sephadex (G-200) gel filtration chromatography was used to purify the Lv II in large quantity. Total lipid extracted from Lv II as well as the embryos belonging to different stages of development were separated into their constituent neutral, glycolipids, and phospholipids, using silicic acid column chromatography. Thin layer chromatography (TLC) was used to isolate the different phospholipids purified from various stages of embryos and Lv II. As many as seven different phospholipids were separated from Lv II and I and IX stage embryos; and whereas thin layer chromatogram of V and VI stage embryos showed six different phospholipids, embryos of VII and VIII stage contained four phospholipid species. Cholesterol, glycolipids, and individual phospholipids isolated from the Lv II and I stage embryo were quantified spectrophotometrically and the results were discussed.
Mol Reprod Dev 1992 Sep
PMID:Purification and characterization of vitellogenin and lipovitellins of the sand crab Emerita asiatica: molecular aspects of crab yolk proteins. 151 Aug 41

X-ray diffraction and equilibrium binding techniques were used to study the effect of cholesterol on membrane binding of the charged 1,4-dihydropyridine (DHP) Ca2+ channel antagonist amlodipine and uncharged isradipine, nimodipine, and nitrendipine. Increases in membrane cholesterol content resulted in a marked decrease in DHP binding to cardiac phospholipid membranes, as expressed by the equilibrium partition coefficient (Kp[mem]). Between a 0:1 and 0.3:1 cholesterol to phospholipid mole ratio, the Kp(mem) values for isradipine, nimodipine, and nitrendipine decreased by greater than 50%, whereas that for amlodipine decreased by only 10%. Electron density profiles calculated from the X-ray diffraction data showed that the time-averaged locations for the DHPs and cholesterol in the membrane overlap, leading to the conclusion that the addition of cholesterol alters the lipid bilayer hydrocarbon core structure in a manner that makes drug partitioning into the membrane less energetically favorable. These data support the idea that drug interactions with the anisotropic membrane environment are complex and may be greatly influenced by cholesterol composition. This effect of cholesterol was also observed for phenylalkylamine (verapamil) and benzothiazepine (diltiazem) Ca2+ channel blockers. The DHP amlodipine had the highest membrane partition coefficient (Kp[mem] greater than 10(4) and the slowest rate of dissociation and was affected least by membrane cholesterol content. The combination of electrostatic and hydrophobic bonding between amlodipine and membrane phospholipid may explain the high affinity of this drug for the membrane bilayer with normal and elevated cholesterol. The results of this study show that cholesterol content differentially affects the membrane-binding properties of the charged DHP amlodipine, compared with other Ca2+ channel blockers. These data help explain the biological distribution of these drugs and the distinct pharmacokinetics of amlodipine versus other Ca2+ channel blockers.
Mol Pharmacol 1992 Feb
PMID:Cholesterol alters the binding of Ca2+ channel blockers to the membrane lipid bilayer. 153 93

The effect of temperature on the velocity of rhodamine phalloidin-labelled F-actin moving in vitro on rabbit skeletal myosin has been studied. Translating actin filaments were visualized by epi-fluorescence in an inverted microscope, equipped with temperature control (+/- 0.2 K) of the stage and objective. Images were recorded in real time at magnifications of 400x or 160x by an intensified CCD camera on video tape. Motion of individual filaments was tracked by hand and velocities determined using frame times recorded simultaneously on the video tape. Velocity changed from 12 microns per second at 42 degrees C to 11 nm per second at 3 degrees C. The Arrhenius plot is non-linear, with the data following a cubic regression curve with no evident breaks or jumps. Data taken over the temperature range from single preparations followed the same curve for both heating and cooling; this indicates reversibility and absence of hysteresis. A hyperbolic model that smoothly translates with temperature between two asymptotic activation energies fits the data above 7 degrees C: these energies are 50(+/- 5) kJ per mole (Q10 = 1.9) at high temperatures and 289(+/- 29) kJ per mole (Q10 = 76.5) at low temperature with a transition temperature of 15.4(+/- 0.6) degrees C. These values are compared with other measurements made in vitro, in solution studies and on muscle fibres. An Arrhenius activation energy of 50 kJ per mole and a transition temperature of 15 degrees C are consistent with previous determinations but 289 kJ per mole is significantly greater than has been seen at low temperatures in other systems. This may indicate a different rate-limiting step in the kinetics of skeletal myosin driving actin filaments in vitro below 15 degrees C. Current determinations of the myosin "step-size" assume that the actin velocity is determined by the rate of ATP hydrolysis; the data confirm similar activation energies above 20 degrees C but they show that the temperature dependencies and activation energies are different at lower temperatures, implying uncoupling of the two processes.
J Mol Biol 1992 Apr 20
PMID:Temperature dependence and Arrhenius activation energy of F-actin velocity generated in vitro by skeletal myosin. 153 50

Branched DNA molecules arise transiently as intermediates in genetic recombination or on extrusion of cruciforms from covalent circular DNA duplexes that contain palindromic sequences. The free energy of these structures relative to normal DNA duplexes is of interest both physically and biologically. Oligonucleotide complexes that can form stable branched structures, DNA junctions, have made it possible to model normally unstable branched states of DNA such as Holliday recombinational intermediates. We present here an evaluation of the free energy of creating four-arm branch points in duplex DNA, using a system of two complementary junctions and four DNA duplexes formed from different combinations of the same set of eight 16-mer strands. The thermodynamics of formation of each branched structure from the matching pair of intact duplexes have been estimated in two experiments. In the first, labeled strands are allowed to partition between duplexes and junctions in a competition assay on polyacrylamide gels. In the second, the heats of forming branched or linear molecules from the component strands have been determined by titration microcalorimetry at several temperatures. Taken together these measurements allow us to determine the standard thermodynamic parameters for the process of creating a branch in an otherwise normal DNA duplex. The free energy for reacting two 16-mer duplexes to yield a four-arm junction in which the branch site is incapable of migrating is + 1.1 (+/- 0.4) kcal mol-1 (at 18 degrees C, 10 mM-Mg2+). Analysis of the distribution of duplex and tetramer products by electrophoresis confirms that the free energy difference between the four duplexes and two junctions is small at this temperature. The associated enthalpy change at 18 degrees C is +27.1 (+/- 1.3) kcal mol-1, while the entropy is +89 (+/- 30) cal K-1 mol-1. The free energy for branching is temperature dependent, with a large unfavorable enthalpy change compensated by a favorable entropy term. Since forming one four-stranded complex from two duplexes should be an entropically unfavorable process, branch formation is likely to be accompanied by significant changes in hydration and ion binding. A significant apparent delta Cp is also observed for the formation of one mole of junction, +0.97 (+/-0.05) kcal deg-1 mol-1.
J Mol Biol 1992 Feb 05
PMID:Thermodynamics of DNA branching. 154 18

Mitochondrial DNA (mtDNA) sequence variation was examined in eight taxa of the African rodent family Bathyergidae, as well as in two taxa representative of the Old-World hystricognathid rodent families Petromyidae and Thryonomyidae. A total of 812 bp, constituting domains I-III of the 12S ribosomal rRNA gene, were compared for each taxon. The high levels of intrafamilial mtDNA sequence divergence observed (average 16.8, range 3.5-23.2) support an ancient origin for the five genera, 20-38 Mya. These data do not support the current subfamilial groupings of the Bathyergidae. The eastern African naked mole-rat, Heterocephalus glaber, is the most basal representative of the family, with the silvery mole-rat, Heliophobius, being the next most basal. South African forms [dune, common, and cape mole-rats (Bathyergus, Cryptomys, and Georychus, respectively)] group together. The independent origin of the common mole-rat, relative to the naked mole-rat, suggests that complex social systems evolved in parallel along different bathyergid lineages. The 12S rRNA gene is not evolving at a higher rate within the rodent lineages, relative to that seen for artiodactyls and primates. Bathyergid rodents appear to fall at an extreme end of the spectrum of mammalian variation, with respect to both transition/transversion ratios and divergence, showing much lower transition/transversion ratios than those previously reported for intrafamilial comparisons.
Mol Biol Evol 1992 Jan
PMID:Nucleotide sequence variation in the mitochondrial 12S rRNA gene and the phylogeny of African mole-rats (Rodentia: Bathyergidae). 155 39

The role of amino functions in the expression of the biological activity of recombinant human TNF (rHuTNF) was studied by chemical modification. rHuTNF is a homotrimer of 17 kD subunits, each of which contains an N-terminal valine and six lysyl residues: two of these lysyl residues are known to be involved in intra- or intersubunit interactions. Chemically reactive amino functions were modified with the N-hydroxysuccinimide ester of acetic acid; modification of amino groups to amide, and the concomitant loss of charge, was monitored by native PAGE. When rHuTNF was reacted with the active ester at increasing mole ratios, up to 12 amino groups per trimer could be modified. When the biological activity of acetylated rHuTNF was determined, a strong correlation between the extent of modification and loss of biological activity was observed. One to three amino groups per trimer could be modified with nearly complete retention (approximately 80-95%) of biological activity; activity was essentially completely destroyed at the highest levels of modification. These results reveal important functions for the amino groups of rHuTNF and significant constraints on strategies involving their modification in development of second-generation-TNF variants.
Mol Immunol 1992 Jan
PMID:The role of amino functions in recombinant human tumor necrosis factor in expression of biological activity. 173 Nov 93

Nine granular cell tumors (GCTs) were studied using the immunoperoxidase technique with a mouse monoclonal antibody to keratan sulfate and a polyclonal antibody to S-100 protein. Various lectins and basic dye stains were also employed. Schwannomas benign and a malignant, a neurofibroma, a leiomyoma, two examples of nevus pigmentosus and a congenital epulis were similarly examined to compare the histochemical reactivities. Tumor cells of all the GCTs reacted intensely with the antibodies to keratan sulfate and S-100 protein. Peripheral nerve bundles and other neurogenic tumors showed stained for S-100 protein but not for keratan sulfate. Basic dye stain indicated the presence of sulfated glycoconjugates in GCTs. Lectin stains demonstrated that GCTs were rich in glycoconjugates but the reactivity patterns for 14 lectins differed between GCTs and normal tissue components. None of the lectins used in this study was specific for GCTs. These results indicate that GCTs contain abundant glycoconjugates and that the monoclonal antibody to keratan sulfate may be an immunohistochemical marker for GCT.
Virchows Arch B Cell Pathol Incl Mol Pathol 1990
PMID:Characterization of glycoconjugates found in granular cell tumors, with special reference to keratan sulfate. 197 Jun 84


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