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 duplex-hairpin interconversion of two DNA decamers, d(CAACGGGTTG) and d(CAACCCGTTG), has been characterized thermodynamically and kinetically by using uv-melting and nmr relaxation methods. Separately, each decamer shows slow exchange between hairpin and duplex conformations. The hairpin conformations have melting points of 47 and 50 degrees C, respectively, and exhibit similar thermodynamic stabilities. The enthalpies of duplex formation, measured by nmr, were found to be very similar (delta HDH = 26 +/- 3 kcal/mole) for both decamers at low salt concentrations (< 50 mM NaCl). However, as the salt concentration was increased the behavior of delta HDH and kinetics is significantly different for each decamer. The d(CAACGGGTTG) decamer forms a duplex containing two central G.G mismatches at high salt and DNA concentration. Based upon the measurement of high interconversion activation energies and a decrease in hairpin formation rate with increasing salt, the interconversion between hairpin and duplex was concluded to proceed by complete strand dissociation. In contrast, the d(CAACCCGTTG) decamer was determined to form a duplex with two centrally located C.C mismatches at pH values less than 6.2, consistent with the formation of a hemiprotonated C+.C mismatch. At pH values greater than 6.4, the hairpin-duplex equilibrium is almost completely shifted toward the hairpin conformation at DNA concentrations of 0.5-7.0 mM and salt concentrations of 10-100 mM. The interconversion of duplex and hairpin conformations was ascertained by means of both kinetic and thermodynamic measurements to proceed by a slightly different mechanism than its complementary decamer. Although the interconversion proceeds by complete strand separation as suggested by high duplex-hairpin interconversion activation enthalpies, the increasing hairpin formation rate with increasing ionic strength as well as the delta HDH dependence on salt indicate that an intermediate internally bulged duplex (no C+.C formation) is stabilized by increasing ionic strength. These data support an interconversion mechanism where an intermediate internally bulged duplex may be the rate limiting step before strand separation.
 ...
PMID:Kinetic and thermodynamic characterization of DNA duplex-hairpin interconversion for two DNA decamers: d(CAACGGGTTG) and d(CAACCCGTTG). 769 64

For a three-component system consisting of solvent (1), polymer or polyelectrolyte (2J), and a nonelectrolyte or electrolyte solute (3), a two-domain description is developed to describe thermodynamic effects of interactions between solute components (2J) and (3). Equilibrium dialysis, which for an electrolyte solute produces the Donnan distribution of ions across a semipermeable membrane, provides a fundamental basis for this two-domain description whose applicability is not restricted, however, to systems where dialysis equilibrium is established. Explicit expressions are obtained for the solute-polymer preferential interaction coefficient gamma 3,2J (nonelectrolyte case) and for gamma +,2J and gamma -,2J, which are corresponding coefficients defined for single (univalent) cations and anions, respectively: gamma +,2J = magnitude of ZJ + gamma -,2J = 0.5(magnitude of ZJ + B-,2J + B+,2J) - B1,2Jm3/m1 Here B+,2J, B-,2J, and B1,2J are defined per mole of species J, respectively, as the number of moles of cation, anion, and water included within the local domains that surround isolated molecules of J; ZJ is the charge on J; m3 is the molal concentration of uniunivalent electrolyte, and m1 = 55.5 mol/kg for water. Incorporating this result into a general thermodynamic description(derived by us elsewhere) of the effects of the activity a+ of excess uniunivalent salt on an equilibrium involving two or more charged species J (each of which is dilute in comparison with the salt) yields:SaKobs bS/d a+ A(r+2J r 2j) A(B+2J B-2 2B12Jm3/m1)where KObS is an equilibrium quotient defined in terms of the molar concentrations of the participants, J, and A denotes astoichio metrically weighted combination of terms pertaining to the reactant(s) and product(s). The derivation presented here does not depend on any particular molecular model for salt-polyelectrolyte (or solute-polymer) interactions; it therefore generalizes our earlier (1978) derivation.
 ...
PMID:Interpretation of preferential interaction coefficients of nonelectrolytes and of electrolyte ions in terms of a two-domain model. 851 73

The lipid composition of the brush border membrane (BBM) or apical plasma membrane of enterocytes is characterized by a remarkably high glycosphingolipid content (glycosphingolipid: phospholipid:neutral lipid mole ratio of about 1:1:1). A manifestation of the high glycolipid content of the BBM is the lipid fluidity which is low compared to other mammalian plasma membranes and related to it a steep flexibility gradient: hydrocarbon chain segments close to the lipid-water interface have quasi-crystalline packing while hydrocarbon chain segments close to the centre of the lipid bilayer behave like a fluid. An important function of the BBM is the absorption of dietary lipids. The absorption of cholesterol from bile salt micelles has been shown to be protein-mediated. The integral membrane protein responsible for this activity has features similar to non-specific lipid transfer proteins. Another remarkable property of the BBM is described here: phospholipids are exchanged between the lipid bilayer of the BBM and the lipid bilayers of small unilamellar egg phosphatidylcholine (PC) vesicles. In the course of this probably 1:1 exchange, endogenous BBM phospholipids move out of the BBM and the lipid loss is compensated by the insertion of exogenous PC from the small unilamellar vesicles. This exchange activity is probably due to the same protein(s) responsible for lipid absorption in this membrane or at least related to the absorptive capacity of the BBM. The unique feature of small intestinal BBM is that the on- and off-rate of certain lipids is remarkably high: the underlying structure of this activity is still unknown.
 ...
PMID:A unique feature of lipid dynamics in small intestinal brush border membrane. 776 68

In a series of related papers, we have recently presented the results of a thermodynamic approach to the conformational transitions of bulk chromatin induced in vitro by different structure-perturbing agents, such as the intercalating dye ethidium bromide or the ionic strength. In all these studies, we took advantage of the capability of differential scanning calorimetry to detect the changes in the melting behavior of the structural domains of chromatin (the linker and the core particle) associated with the order-disorder transitions. This technique also revealed that the higher-order structure undergoes a catastrophic decondensation process in the course of the transformation of rat hepatocytes as well as of cultured cells. Therefore, several questions arose concerning the biological function (if any) of the changes in the degree of condensation of bulk chromatin, as well as the mechanism of transition and the nature of the modulating agents. In this paper, we report a thermodynamic analysis of the reconstitution of H1-depleted calf thymus chromatin with the purpose of establishing (1) the binding mode of H1 and (2) the energetics and cooperativity of the transition from the unfolded to the condensed state. When H1 is progressively extracted from calf thymus nuclei by high-salt treatment, the endotherm at 107 degrees C, characteristic of the core particles interacting within condensed domains, converts into the thermal transition at 90 degrees C, resulting from the denaturation of noninteracting core particles. Binding of H1 fully restores the thermal profile of native chromatin. Analysis of H1 association shows that binding occurs at independent sites with KA = (3.67 +/- 0.60) x 10(4) M-1 and each site comprising 180 +/- 10 bp. The experimental dependence of the fraction of condensed chromatin on R, the moles of bound H1 per nucleosome mole, was compared with a simple thermodynamic model for the conformational change. This analysis yields a value of -5 kcal per nucleosome mole for the interaction free energy of nucleosomes within the ordered state. The process of condensation, is not, however, a highly cooperative (all-or-none) one, as expected from a consideration of the solenoidal model for the 30 nm fiber. Rather, nucleation of the helical state involves the face-to-face interaction between consecutive core particles, and the growth is largely determined by the mergence and rearrangement of neighboring clusters of helically arrayed nucleosomes.
 ...
PMID:Role of H1 in chromatin folding. A thermodynamic study of chromatin reconstitution by differential scanning calorimetry. 781 11

Mixed micellar electrokinetic chromatography (MMEKC) using mixtures of bile salt surfactants and/or sodium dodecyl sulfate (SDS) was employed to separate a group of corticosteroids. Resolution of electrokinetic chromatography (EKC) can be greatly enhanced by the use of mixed micellar systems due to the fact that the composition of the mixed micelles has a great influence on retention, selectivity and the size of the elution window. By combining surfactants with different structural properties, solute-micelle interactions were manipulated in order to elicit specific separations. Various combinations of bile salts and/or SDS at different mole fractions as well as total micelle concentrations were used in order to enhance the resolution of corticosteroid separations. Large changes in retention and selectivity were observed that often resulted in frequent variations in elution order. In addition, the composition of mixed micellar systems had a great influence on the elution window in EKC, as measured by the ratio of tmc/teo. Addition of SDS to the mixtures of bile salt micelles resulted in significant extension of the elution window and subsequently improvement in resolution. A separation of seventeen corticosteroids was achieved. Finally, MMEKC was applied in order to separate the steroidal components of a mixture of three anti-inflammatory creams.
 ...
PMID:Mixed micellar electrokinetic chromatography of corticosteroids. 789 15

The hairpin-duplex equilibria of the dodecamer d-AAGCTTAAGCTT and interaction of the duplex form with a pentapeptide, KGWGK, has been studied. UV thermal transitions are monophasic at low salt but biphasic at higher salt concentrations. At 10(-5) M or less oligomer concentration biphasic melting curves persist till 900 mM NaCl. The d(Tm)/d log(Na+) for the duplex form is 12 degrees C and for the hairpin is 18 degrees C. The delta H and delta S values for duplex formation are low (-25 K cal/mole and -59 Cal/mole respectively). KGWGK binds to the duplex form with a binding constant K = 3.4 x 10(5)M-1 measured from fluorescence quenching of tryptophan. These unusual results are markedly different from that reported for d-AGATCTAGATCT (Biochemistry 31, 6241-6245) and are discussed in terms of sequence dependence of loop folding and cruciform extrusion pathway of hairpin formation.
 ...
PMID:Hairpin formation in d-AAGCTTAAGCTT under high salt conditions shows unusual properties. 794 59

For order-disorder transitions of double- and triple-stranded nucleic acid helices, the midpoint temperatures Tm depend strongly on a +/-, the mean ionic activity of uniunivalent salt. Experimental determinations of dTm/d ln a +/- and of the enthalpy change (delta H(o)) accompanying the transition in excess salt permit evaluation of delta gamma, the stoichiometrically weighted combination of preferential interaction coefficients, each of which reflects thermodynamic effects of interactions of salt ions with a reactant or product of the conformational transition (formula; see text) Here delta H(o) is defined per mole of nucleotide by analogy to delta gamma. Application of Eq. 1 to experimental values of delta H(o) and Tm yields values of delta gamma for the denaturation of B-DNA over the range of NaCl concentrations 0.01-0.20 M (Privalov et al. (1969), Biopolymers 8,559) and for each of four order-disorder transitions of poly rA.(poly rU)n, n = 1, 2 over the range of NaCl concentrations 0.01-1.0 M (Krakauer and Sturtevant (1968), Biopolymers 6, 491). For denaturation of duplexes and triplexes, delta gamma is negative and not significantly dependent on a +/-, but delta gamma is positive and dependent on a +/- for the disproportionation transition of poly rA.poly rU duplexes. Quantitative interpretations of these trends and magnitudes of delta gamma in terms of coulombic and excluded volume effects are obtained by fitting separately each of the two sets of thermodynamic data using Eq. 1 with delta gamma PB evaluated from the cylindrically symmetric Poisson-Boltzmann (PB) equation for a standard model of salt-polyelectrolyte solutions. The only structural parameters required by this model are: b, the mean axial distance between the projections of adjacent polyion charges onto the cylindrical axis; and a, the mean distance of closest approach between a salt ion center and the cylindrical axis. Fixing bMS and aMS for the multi-stranded (ordered) conformations, we determined the corresponding best fitted values of bSS and aSS for single-stranded RNA and DNA. The resulting best fitted values of aSS are systematically less than aDS by 2-4 A. Uncertainty in the best-fitted values of bSS is significantly lower than in the aSS, because bMS is known with relatively high precision and because the larger uncertainty in aMS has a relatively small effect on the best-fitted values of bSS:bSS = 3.2 +/- 0.6 A for single-stranded poly rA and poly rU; and bSS = 3.4 +/- 0.2 A for single-stranded DNA. These values are approximately one-halt of those expected for a fully extended single-stranded conformation. With the best fitted values of ass and bss, our calculations of delta gamma PB are in close quantitative agreement with experimental observations on each of five nucleic acid order-disorder transitions.
 ...
PMID:Conformational transitions of duplex and triplex nucleic acid helices: thermodynamic analysis of effects of salt concentration on stability using preferential interaction coefficients. 794 95

Bovine lens alpha-crystallin inhibited both porcine pancreatic elastase (PPE) and human neutrophil elastase (HNE), but not in the same manner. PPE was immediately inhibited with a stoichiometry of 10 moles of PPE inhibited per mole of alpha-crystallin. The inhibition was markedly decreased by the addition of even low levels of salts. The inhibition was transient, as PPE activity returned to normal with a t1/2 of 30 min even in low salt. HNE required a short preincubation to show maximum inhibition with a stoichiometry of approximately one mole of HNE inhibited per mole of alpha-crystallin. The inhibition of HNE was only slightly decreased by the addition of 0.1 M salt, and HNE activity returned slowly exhibiting a t1/2 of 30 hrs under these conditions. The inhibition of each enzyme by alpha-crystallin was evaluated by Dixon plots giving Ki values of 1.5 nM for PPE and 0.25 nM for HNE. DFP-trypsin was able to compete with PPE for binding to alpha-crystallin and cause the release of PPE already bound to alpha-crystallin. The inhibition of HNE, however, was unaffected by the addition of DFP-trypsin. A mixture of HNE and alpha-crystallin in 0.1 M NaCl was incubated at 25 degrees C for 6 hours. Aliquots showed a slow, continuous cleavage of the alpha-crystallin subunits by SDS-PAGE, but little or no increase in HNE activity.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A comparison of the inhibition of porcine pancreatic elastase and human neutrophil elastase by alpha-crystallin. 795 8

Extremely halophilic archaebacteria which require high salt concentrations for growth and survival contain glycerol diether analogues of phospholipids and sulfated glycolipids as major membrane polar lipids. A non-alkaliphilic, non-pigmented rod-shaped extreme halophile, isolated from sea sand in Japan and designated 'strain 172', was found to contain two phospholipids, phosphatidylglycerol (PG) and phosphatidylglyceromethylphosphate (PGP-Me), derived from both C20-C20- and C20-C25-glycerol diethers, and a novel major glycolipid (designated SGL-X). This glycolipid has been identified as a bis-sulfated diglycosyl C20-C20- or C20-C25-glycerol diether, on the basis of its TLC mobility, positive-staining behavior with sugar and sulfate-staining reagents, its mole ratio sulfate/glycolipid = 2.2, and by spectrometric analysis (IR and FAB-MS) of the intact and the desulfated SGL-X. The sugars were identified as mannose and glucose, after acid hydrolysis of SGL-X, by paper chromatography of the free sugars and GC-MS of the derivatized sugars (alditol acetates). Permethylation analysis and 1H- and 13C-NMR analysis established the position and configuration of the sugar linkages and the positions of the sulfate groups. The final structure of SGL-X (now designated S2-DGD-1) is proposed to be: 2,3-diphytanyl- or phytanyl-sesterterpenyl-1-[2,6-(HSO3)2-alpha-Manp-1--> 2- Glcp]-sn-glycerol. This lipid is the first bis-sulfated glycolipid to be reported in extremely halophilic archaebacteria, and is the first in the biosphere that possesses two sulfate groups attached to the same monosaccaride.
 ...
PMID:Polar lipids of a non-alkaliphilic extremely halophilic archaebacterium strain 172: a novel bis-sulfated glycolipid. 806 33

A polymerizable gel superaggregate has been formed from low concentrations (6 mM) of phospholipid mixtures of polymerizable 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine and 1,2-bis(dinonoyl)-sn-glycero-3-phosphocholine. Transmission electron microscopy (TEM) revealed that the superaggregate structure consisted of a network of twisted, braided fibers and that the pore size of the gel ranged from 0.1 to 1.0 micron. TEM of gel plated with Ni revealed that the width of the fibers was 280 A. Optical microscopy demonstrated that the onset of the gel phase occurred at mole fraction 0.43 DNPC in the absence of salt and 0.36 in the presence of 0.25 M NaCl. Polymerization did not affect the morphology of the gel but did increase its temperature stability.
 ...
PMID:Formation and properties of a network gel formed from mixtures of diacetylenic and short-chain phosphocholine lipids. 807 70


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