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Results for “Structural changes”

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At least 19 recordsLinked to original sources

PubMed1977

Chromosomes 1 in 14 ovarian cancers. Heterochromatin variants and structural changes.

Structurally rearranged chromosomes 1 were found in 9 out of 14 ovarian carcinomas and may also have been present in three others. In the remaining two, pericentric inversions involving the heterochromatic regions of chromosomes 1 were seen, and were also identified in one of the chromosomes 1 in the patient's normal cells (lymphocytes). Altogether, heterochromatin variants (variation in size and/or the presence of a pericentric inversion) were seen in the tumour cells of eight cases, and one or both types of variation were identified in the normal cells of six of these. The possibility of an association between the presence of chromosome 1 heterochromatin variants as a constitutional anomaly, a liability to ovarian (and perhaps other forms of) cancer and structural changes involving the chromosomes 1 in the tumour cells is considered.

Adult↗

PubMed1992

Pathophysiology of cardiovascular structural changes in hypertension.

Hypertrophic adaptation of the left ventricle and blood vessels is a prominent feature of established essential hypertension. Presence of left ventricular hypertrophy in hypertension increases, independently of other risk factors, the risk for a number of the most important cardiovascular hypertensive complications. Available evidence indicates that left ventricular hypertrophy develops in close parallel with the peripheral vascular changes. Structural involvement can be detected already in early phases of borderline hypertension. The pathophysiology of structural changes in hypertension appears to be dependent on a complex interplay between genetic, hemodynamic, and humoral-metabolic factors.

Animals↗

PubMed1992

Secondary structural changes of metmyoglobin and apomyoglobin in anionic and cationic surfactant solutions: effect of the hydrophobic chain length of the surfactants on the structural changes.

Secondary structural changes of metmyoglobin and apomyoglobin were examined in solutions of sodium alkylsulfates with hydrocarbon numbers of 8 and 12, and alkyltrimethylammonium bromides with hydrocarbon numbers of 10, 12, 14, and 16. The relative proportion of alpha-helical structure was estimated by the curve-fitting method of circular dichroic spectrum. The helical proportions of metmyoglobin and apomyoglobin were 82 and 63%, respectively. The shorter the hydrocarbon chain the surfactant had, the higher the concentration necessary to disrupt the secondary structures of these proteins. However, the helical proportion had a tendency to decrease down to lower values in solutions of the cationic surfactants with short hydrophobic groups. On the other hand, the alpha-helical structure of apomyoglobin was disrupted in lower concentrations of each cationic surfactant than that of metmyoglobin, although the disruptions of the same structures in both the proteins occurred in the same concentration range of each anionic surfactant. It appeared likely that the removal of the heme group unstabilized the myoglobin conformation only in the cationic surfactant solutions.

Anions↗

PubMed1990

Large-scale structural changes in the sarcoplasmic reticulum ATPase appear essential for calcium transport.

Model refinement calculations utilizing the results from time-resolved x-ray diffraction studies indicate that specific, large-scale changes (i.e., structural changes over a large length scale or long range) occur throughout the cylindrically averaged profile structure of the sarcoplasmic reticulum ATPase upon its phosphorylation during calcium active transport. Several physical-chemical factors, all of which slow the kinetics of phosphoenzyme formation, induce specific, large-scale changes throughout the profile structure of the unphosphorylated enzyme that in general are opposite to those observed upon phosphorylation. These results suggest that such large-scale structural changes in the ATPase occurring upon its phosphorylation are required for its calcium transport function.

Biological Transport, Active↗

PubMed1978

Ion movements during energy-linked mitochondrial structural changes.

The structure of isolated rat liver mitochondria has been observed in the electron microscope following incubation of the mitochondria in vitro under a variety of conditions. The results show that ultrastructural changes are only associated with the energization and deenergization of isolated mitochondria if the composition of the incubation medium permits ion movements in or out of the matrix. The mechanism of energy coupling does not appear to depend on these major mitochondrial structural changes. The addition of low levels of valinomycin greatly increases the rate at which the matrix compartment swells and shrinks on energization and deenergization even at low K+ concentrations.

Adenosine Diphosphate↗

PubMed1991

Application of linear free energy relations to protein conformational changes: the quaternary structural change of hemoglobin.

The transition state for the R in equilibrium with T quaternary conformational change of hemoglobin has thermodynamic properties much closer to those of the R conformation than to those of the T conformation. This finding is based on a comparison of activation and equilibrium enthalpy and entropy changes and on the observation of a linear free energy relationship between quaternary rate and equilibrium constants. A previous theoretical study [Janin, J. & Wodak, S. J. (1985) Biopolymers 24, 509-526], using a highly simplified energy function, suggests that the R-like transition state is the result of a reaction pathway with the maximum buried surface area between alpha beta dimers.

Allosteric Regulation↗

PubMed1992

Reversal of cardiovascular structural changes when treating essential hypertension. The importance of the renin-angiotensin-aldosterone system.

Our study attempted to evaluate the importance of changes in the circulating renin-angiotensin-aldosterone system (RAAS) and in hemodynamics in relation to observed changes in cardiovascular structure. We studied previously untreated men (n = 28) with essential nonmalignant hypertension and a supine casual diastolic blood pressure > 95 mm Hg on three to four separate (> 1-week interval) occasions measured in triplicate. We used intraarterial blood pressure, dye-dilution technique, plethysmography (hands), eye-ground photos, M-mode echocardiography, radio immunoassays, and multiple regression analysis. Patients were randomized to 6 months of double-blind treatment with either enalapril or hydrochlorothiazide, following 4 to 6 weeks on placebo. We found that enalapril blocked the plasma angiotensin converting enzyme (ACE) with a secondary increment in plasma renin activity (PRA) and reductions in angiotensin II (AII) and aldosterone. Blood pressure was lowered through a reduction in total peripheral resistance (TPR). Hydrochlorothiazide increased PRA, AII, and aldosterone, and lowered blood pressure mainly through a reduction in cardiac output. Enalapril was significantly more effective than hydrochlorothiazide in reversing structural changes in the retinal and hand vasculature as well as in the heart. A reduction in cardiac hypertrophy was seen even in the occasional enalapril-treated patient, in whom little or no reduction in blood pressure occurred. In the stepwise regression analyses, the changes in retinal and hand vascular structure were most strongly related to various changes in the RAAS, explaining 15 to 34% of the variance. For the changes in cardiac structure, the type of therapy (enalapril or hydrochlorothiazide) appeared to be the most important factor, explaining between 29 and 50% of the variance. The changes in cardiac structure were even more strongly related to changes in the RAAS for the enalapril treated patients and explained up to 55% of the variance in cardiac structure. It can be concluded that the reversal of structural vascular changes during antihypertensive therapy was more dependent on the blockade of the RAAS than on lowering of the blood pressure.

Blood Pressure↗

PubMed1990

Use of analytical gel chromatography to analyze tertiary and quaternary structural changes in E. coli aspartate transcarbamylase.

E. coli aspartate transcarbamylase (ATCase) is a large (310 kDa) protein that undergoes major changes in quaternary structure when substrates and regulatory nucleotides bind. We have used analytical gel chromatography to detect quaternary structure changes in both the holoenzyme and its catalytic subunit (c3), to characterize the quaternary structure of single site mutant proteins and to monitor urea-induced dissociation and unfolding of c3. Binding of the bisubstrate analog PALA (N-(phosphonacetyl)-L-aspartate) to ATCase and c3 has been shown to alter s20.w by -3.3% and + 1.4%, respectively [Howlett, G.J. and Schachman, H.K. (1977), Biochemistry 23, 5077-5083]. The corresponding changes in the chromatographic partition coefficient (sigma) are -2.6 +/- 0.3% and 5.5 +/- 1.9% on Sephacryl S400HR and S200, respectively. Partition coefficients of mutant ATCases with single site mutations in the c chain differ from those of the wild-type protein by +/- 0.5% in small zone experiments; for example, mutations Arg 269----Gly and Glu 239----Gln alter the partition coefficient by 0.4% and -0.5%, respectively. The partition coefficient of mutant Glu 50----Gln is identical to the wild type enzyme. In the presence of saturating PALA, partition coefficients of Glu 50----Gln and Arg 269----Gly, but not Glu 239----Gln are identical to those of the wild type. Results for Glu 239----Gln are consistent with measurements of activity, small angle X-ray scattering and sedimentation coefficient that indicate that mutations at this site shift the quaternary structure towards the R state [Ladjimi and Kantrowitz (1988), Biochemistry 27, 276-83; Vachette and Hervé, cited by Kantrowitz and Lipscomb (1988), Science 241, 669-674; Newell and Schachman (1988), FASEB J. 2, A551]. Results for Glu 50----Gln are also consistent with measurements of activity (Ladjimi et al. (1988), Biochemistry 27, 268-276). The changes in tertiary and quaternary structure that result from urea-induced denaturation of c3 result in larger changes in the partition coefficient. Dissociation into folded monomers in 1-1.75 M urea is accompanied by a 4.6% increase in partition coefficient, while denaturation at greater than 5 M urea gives rise to a 43% decrease on S-300 Sephacryl. The bisubstrate analog PALA suppresses dissociation and increases the cooperativity of the unfolding reaction.

Aspartate Carbamoyltransferase↗

PubMed1979

Salt-and histone H1-induced structural changes of reconstituted minichromosomes.

Structural changes of reconstituted SV 40 minichromosomes have been studied in relation to the salt concentration and addition of histone H1 by sedimentation and electron microscopy. Sedimentation data are represented as functions of the NaCl concentration and the Debye-Hückel electrostatic screening radius 1/alpha. The latter representation which proved to provide more information revealed three structural states of the SV 40 reconstitutes which can be additionally characterized by electron microscopy as follows: Expanded or relaxed conformation including free DNA spacers between the nucleosomes at low salt concentration (approx. 0.001 M-0.05 M NaCl), increasing condensation at moderate salt concentration (approx. 0.05 M-0.3 M NaCl) and expansion of this condensed state above approx. 0.3 M NaCl. The condensation of the reconstitutes at moderate salt concentration does not require the presence of histone H1. H1 seems to stabilize the condensed state against electrostatic expansion. The condensation might be promoted by salt-dependent conformational changes of naked superhelical DNA as revealed by sedimentation measurements.

Chromosomes↗

PubMed1979

Proton nuclear magnetic resonance investigation of structural changes associated with cooperative oxygenation of human adult hemoglobin.

The structural changes associated with cooperative oxygenation of human adult hemoglobin as a function of oxygen saturation in aqueous media at neutral pH and at 25-27 degrees C have been investigated by high-resolution proton nuclear magnetic resonance spectroscopy at 250 and 360 MHz. By monitoring the intensities of two hyperfine shifted proton resonances (at about -12 and -18 ppm from H(2)O) and two exchangeable proton resonances (at about -6.4 and -9.4 ppm from H(2)O) as a function of oxygenation, the amount of oxygen bound to the alpha and beta chains of a hemoglobin molecule can be determined and the relationship between tertiary and quaternary structural changes under a given set of experimental conditions can be investigated. These results suggest that: (i) in the absence of organic phosphates, there is no preferential O(2) binding to the alpha or beta chains; (ii) in the presence of organic phosphates, the alpha hemes have a higher affinity for O(2) as compared to the beta hemes; (iii) the ligand-induced structural changes in the hemoglobin molecule are not concerted; and (iv) some cooperativity must be present within the deoxy quaternary state during the oxygenation process. The variations of the exchangeable proton resonances as a function of oxygenation strongly suggest that the breaking of one or more inter- or intrasubunit linkages of a ligated subunit can affect similar linkages in unligated subunits within a tetrameric hemoglobin molecule. Thus, the present results show that two-state allosteric models are not adequate to describe the cooperative oxygenation of hemoglobin. In addition, the present results provide direct correlation to the ligand-induced structural changes (such as in the heme pockets and subunit interfaces) observed to occur in the crystals of deoxy- and oxy-like hemoglobin molecules and in the solution state.

Allosteric Regulation↗

PubMed1977

Effects of dimethyl sulfoxide on Tetrahymena pyriformis GL. Fine structural changes and their reversibility.

Fine-structural changes are induced in Tetrahymena by exposure to 7.5% dimethyl sulfoxide (DMSO) in the presence of growth medium. Some of these changes (nucleolar, mitochondrial, peroxisomal) resemble those seen during starvation, in agreement with the previously reported inhibitory effect of DMSO on food-vacuole formation; however, changes such as helical formations of polyribosomes indicate additional internal actions of the reagent. The effects vary to some extent within the same group of cells, suggesting that sensitivity to the reagent may differ with the stage in the cell cycle. The structural changes induced by a 1-hr exposure to DMSO are reversible, but recovery of the cells after removal of the reagent is slower than that seen after starvation. The observations suggest that the recovery is associated with renewed synthesis.

Animals↗

PubMedDate not supplied

[Spin label study of structural changes at different depths of phospholipid membranes after their peroxidation].

Changes of structural organization of liposomal phospholipid membranes, after their Fe2+-induced peroxidation were studied at different depth using nitroxyl derivatives of stearic acid. It was established that during Fe2+-induced lipid peroxidation a strong rise in lipid polarity accompanied with immobilization of acyl chains of phospholipids at the depth of 0.6-0.8 nm from the surface was measured. At the same time no significant changes in the structural organization were seen at the depth of 20-22 nm.

Electron Spin Resonance Spectroscopy↗

PubMed1992

Structural change of the thorax in chronic obstructive pulmonary disease.

This study examines structural changes of the thorax in hyperinflated subjects with chronic obstructive pulmonary disease (COPD). Age-matched normal subjects were used for comparison. Thoracic dimensions were determined using anteroposterior and lateral chest radiographs performed at total lung capacity, functional residual capacity, and residual volume. Rib cage dimensions (lateral diameter, rib angle, anteroposterior diameter) and diaphragm position were determined at each lung volume. There were no significant differences in rib cage dimension between the COPD and normal subjects for all lung volumes. In contrast, the diaphragm was significantly lower in the COPD subjects. The change of rib cage dimensions in the COPD subjects (for a similar volume change) was not different from that in normal subjects, whereas the change of diaphragm position in the COPD subjects (for a similar volume change) was reduced. In conclusion, the primary structural change of the thorax in COPD with chronic hyperinflation is confined to the diaphragm, with no appreciable structural change in the rib cage.

Aged↗

PubMed1989

ATP-induced structural change in myosin subfragment-1 revealed by the location of protease cleavage sites on the primary structure.

To understand the nature of the ATP-induced structural change in myosin subfragment-1, rabbit and chicken skeletal subfragments-1s were cleaved by various proteolytic enzymes in the absence, and in the presence, of ATP and the exact locations of the cleavage sites that were affected by ATP were determined from the amino end analysis of fragments by the use of a protein sequencer. It was found that subtilisin cleaved a site between Gln27 and Asn28 of rabbit subfragment-1 and between Gln28 and Asn29 of chicken subfragment-1 only in the presence of ATP. Thermolysin cleaved a site between Pro31 and Phe32 of chicken subfragment-1 in the presence of ATP, but the same site of rabbit subfragment-1 was not cleaved. The location of these sites is quite similar to the ATP-induced chymotryptic cleavage site of chicken gizzard heavy meromyosin, between Trp29 and Ser30 as reported by others. It is suggested, therefore, that the structure and the ATP-induced structural change in the regions are similar in these subfragment-1s. ATP also changes the cleavage rate of the 26K-50K junction by many proteases. Exact cleavage sites were determined and the relationship between their location and the suppression or the enhancement by ATP of the cleavage was studied. It was found that the cleavage sites were restricted to a quite narrow region and only the cleavage by thermolysin that attacked the middle of the region was enhanced by ATP. The distribution of the cleavage sites and the effect of ATP suggest that ATP induces drastic structural change at the middle of the 26K-50K junction region. The region attacked easily by many proteases coincided very well with a hydrophilic region indicated by the hydropathy index. The region probably protrudes outside and is, therefore, easily attacked by many proteases.

Adenosine Triphosphate↗

PubMed1991

19F NMR studies of the D-galactose chemosensory receptor. 1. Sugar binding yields a global structural change.

The Escherichia coli D-galactose and D-glucose receptor is an aqueous sugar-binding protein and the first component in the distinct chemosensory and transport pathways for these sugars. Activation of the receptor occurs when the sugar binds and induces a conformational change, which in turn enables docking to specific membrane proteins. Only the structure of the activated receptor containing bound D-glucose is known. To investigate the sugar-induced structural change, we have used 19F NMR to probe 12 sites widely distributed in the receptor molecule. Five sites are tryptophan positions probed by incorporation of 5-fluorotryptophan; the resulting 19F NMR resonances were assigned by site-directed mutagenesis. The other seven sites are phenylalanine positions probed by incorporation of 3-fluorophenylalanine. Sugar binding to the substrate binding cleft was observed to trigger a global structural change detected via 19F NMR frequency shifts at 10 of the 12 labeled sites. Two of the altered sites lie in the substrate binding cleft in van der Waals contact with the bound sugar molecule. The other eight altered sites, specifically two tryptophans and six phenylalanines distributed equally between the two receptor domains, are distant from the cleft and therefore experience allosteric structural changes upon sugar binding. The results are consistent with a model in which multiple secondary structural elements, known to extend between the substrate cleft and the protein surface, undergo shifts in their average positions upon sugar binding to the cleft. Such structural coupling provides a mechanism by which sugar binding to the substrate cleft can cause structural changes at one or more docking sites on the receptor surface.

Carbohydrate Metabolism↗

PubMed1977

Structural changes and fluctuations of proteins. I. A statistical thermodynamic model.

A general theory of the structural changes and fluctuations of proteins has been proposed based on statistical thermodynamic considerations at the chain level. The "structure" of protein was assumed to be characterized by the state of secondary bonds between unique pairs of specific sites on peptide chains. Every secondary bond changes between the bonded and unbonded states by thermal agitation and the "structure" is continuously fluctuating. The free energy of the "structural state" that is defined by the fraction of secondary bonds in the bonded state has been expressed by the bond energy, the cooperative interaction between bonds, the mixing entropy of bonds, and the entropy of polypeptide chains. The most probable "structural state" can be simply determined by graphical analysis and the effect of temperature or solvent composition on it is discussed. The temperature dependence of the free energy, the probability distribution of structural states and the specific heat have been calculted for two examples of structural change. The theory predicts two different types of structural changes from the ordered to disorderd state, a "structured transition" and a "gradual structural change" with rising temperature. In the "structural transition", the probability distribution has two maxima in the temperature range of transition. In the "gradual structural change", the probabilty distribution has only one maximum during the change. A considerable fraction of secondary bonds is in the unbounded state and is always fluctuating even in the ordered state at room temperature. Such structural flucutations in a single protein molecule have been discussed quantitatively. The theory is extended to include small molecules which bind to the protein molecule and affect the structural state. The changes of structural state caused by specific and non-specific binding and allosteric effects are explained in a unified manner.

Chemical Phenomena↗

PubMed1990

Salt-dependent structure change and ion binding in cytochrome c studied by two-dimensional proton NMR.

To search for salt-dependent structure changes that might help to explain physicochemical differences observed in previous solution studies, two-dimensional proton NMR spectra of reduced and oxidized cytochrome c were recorded at relatively high and low salt concentrations. The results rule out substantial ionic strength dependent structure change in either redox form over the salt concentrations tested (5 mM phosphate to 5 mM phosphate plus 200 mM NaCl, at pH 7). Chemical shift changes were found for several residues within a limited segment of the oxidized protein, most prominently in the sequence Lys-86, Lys-87, Lys-88, Thr-89. A salt-dependent binding of phosphate anion(s) at this site, as observed earlier by others, is indicated. The binding of one or two phosphates at the cytochrome c surface can explain earlier small-angle X-ray scattering observations of an increase in the calculated radius of gyration of the oxidized protein at the same low-salt condition used here. Other observations, by ultraviolet resonance Raman and 1D NMR spectroscopies, of salt-dependent changes could not be corroborated, but may depend on the still lower salt used and the absence of phosphate. The results obtained support the view that the absence of sizeable redox-dependent structure change observed in X-ray and NMR studies at varying salt conditions is characteristic of the protein at all salt conditions above the low millimolar range. Physicochemical differences between oxidized and reduced cytochrome c apparently represent differences in stability without patent structure change.

Amino Acid Sequence↗

PubMed1989

Fourier transform infrared evidence for proline structural changes during the bacteriorhodopsin photocycle.

Structural changes involving bacteriohodopsin proline residues have been investigated by Fourier transform infrared difference spectroscopy. Bacteriohodopsin (bR)-producing Halobacteria halobium were grown on a stringent medium containing either ring-perdeuterated proline or 15N-labeled proline. Comparison of the difference spectra obtained from the photoreactions of these labeled bR samples with those for unlabeled bR has led to the assignment of peaks due to proline vibrations. [proline-N15]bR exhibited a 15-cm-1 isotopic downshift of peaks in the 1420- to 1440-cm-1 region of the bR----K and bR----M difference spectra as well as a similar downshift of peaks found in the absolute absorption spectrum of bR. In contrast, [proline-D7]bR did not cause shifts in this region of the difference spectra. These results indicate that one or more prolines undergo a structural rearrangement during the bR photocycle involving the Xaa-Pro C--N peptide bond. This change may be directly coupled to the light-induced isomerization of the retinal chromophore from all-trans-retinal to 13-cis-retinal.

Bacteriorhodopsins↗