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1.
Ol’ha O. Brovarets’ Roman O. Zhurakivsky Dmytro M. Hovorun 《Journal of molecular modeling》2013,19(10):4223-4237
Combining quantum-mechanical (QM) calculations with quantum theory of atoms in molecules (QTAIM) and using the methodology of sweeps of the energetic, electron-topological, geometric and polar parameters, which describe the course of the tautomerization along the intrinsic reaction coordinate (IRC), we showed for the first time that the biologically important A?A* base pair (Cs symmetry) formed by the amino and imino tautomers of adenine (A) tautomerizes via asynchronous concerted double proton transfer (DPT) through a transition state (TS), which is the A+?A? zwitterion with the separated charge, with Cs symmetry. The nine key points, which can be considered as electron-topological “fingerprints” of the asynchronous concerted A?A*?A*?A tautomerization process via the DPT, were detected and completely investigated along the IRC of the A?A*?A*?A tautomerization. Based on the sweeps of the H-bond energies, it was found that intermolecular antiparallel N6Н?N6 (7.01 kcal mol?1) and N1H?N1 (6.88 kcal mol?1) H-bonds are significantly cooperative and mutually reinforce each other. It was shown for the first time that the A?A*?A*?A tautomerization is assisted by the third C2H?HC2 dihydrogen bond (DHB), which, in contrast to the two others N6H?N6 and N1H?N1 H-bonds, exists within the IRC range from ?2.92 to 2.92 Å. The DHB cooperatively strengthens, reaching its maximum energy 0.42 kcal mol?1 at IRC?=??0.52 Å and minimum energy 0.25 kcal mol?1 at IRC?=??2.92 Å, and is accompanied by strengthening of the two other aforementioned classical H-bonds. We established that the C2H?HC2 DHB completely satisfies the electron-topological criteria for H-bonding, in particular Bader’s and all eight “two-molecule” Koch and Popelier’s criteria. The positive value of the Grunenberg’s compliance constant (5.203 Å/mdyn) at the TSA?A*?A*?A proves that the C2H?HC2 DHB is a stabilizing interaction. NBO analysis predicts transfer of charge from σ(C2–H) bonding orbital to σ*(H–C2) anti-bonding orbital; at this point, the stabilization energy E(2) is equal to 0.19 kcal mol?1 at the TSA?A*?A*?A. 相似文献
2.
Oleh V. Lushchak Dmytro V. Gospodaryov Ihor S. Yurkevych Kenneth B. Storey 《Archives of insect biochemistry and physiology》2016,91(1):52-63
Aging is often associated with accumulation of oxidative damage in proteins and lipids. However, some studies do not support this view, raising the question of whether high levels of oxidative damage are associated with lifespan. In the current investigation, Drosophila melanogaster flies were kept on diets with 2 or 10% of either glucose or fructose. The lifespan, fecundity, and feeding as well as amounts of protein carbonyls (PC) and lipid peroxides (LOOH), activities of superoxide dismutase (SOD), catalase, glutathione‐S‐transferase (GST), and glutathione reductase activity of thioredoxin reductase (TrxR) were measured in “young” (10‐day old) and “aged” (50‐day old) flies. Flies maintained on diets with 10% carbohydrate lived longer than those on the 2% diets. However, neither lifespan nor fecundity was affected by the type of carbohydrate. The amount of PC was unaffected by diet and age, whereas flies fed on diets with 10% carbohydrate had about fivefold higher amounts of LOOH compared to flies maintained on the 2% carbohydrate diets. Catalase activity was significantly lower in flies fed on diets with 10% carbohydrates compared to flies on 2% carbohydrate diets. The activities of SOD, GST, and TrxR were not affected by the diet or age of the flies. The higher levels of LOOH in flies maintained on 10% carbohydrate did not reduce their lifespan, from which we infer that oxidative damage to only one class of biomolecules, particularly lipids, is not sufficient to influence lifespan. 相似文献
3.
Primary, secondary and higher-order structures of downstream elements of mammalian pre-mRNA polyadenylation signals [poly(A) signals] are re viewed. We have carried out a detailed analysis on our database of 244 human pre-mRNA poly(A) signals in order to characterize elements in their downstream regions. We suggest that the downstream region of the mammalian pre-mRNA poly(A) signal consists of various simple elements located at different distances from each other. Thus, the downstream region is not described by any precise consensus. Searching our database, we found that ~80% of pre-mRNAs with the AAUAAA or AUUAAA core upstream elements contain simple downstream elements, consisting of U-rich and/or 2GU/U tracts, the former occurring ~2-fold more often than the latter. Approximately one-third of the pre-mRNAs analyzed here contain sequences that may form G-quadruplexes. A substantial number of these sequences are located immediately downstream of the poly(A) signal. A possible role of G-rich sequences in the polyadenylation process is discussed. A model of the secondary structure of the SV40 late pre-mRNA poly(A) signal downstream region is presented. 相似文献
4.
Lance-Jones C Omelchenko N Bailis A Lynch S Sharma K 《Development (Cambridge, England)》2001,128(12):2255-2268
We have used Hoxd10 expression as a primary marker of the lumbosacral region to examine the early programming of regional characteristics within the posterior spinal cord of the chick embryo. Hoxd10 is uniquely expressed at a high level in the lumbosacral cord, from the earliest stages of motor column formation through stages of motoneuron axon outgrowth. To define the time period when this gene pattern is determined, we assessed Hoxd10 expression after transposition of lumbosacral and thoracic segments at early neural tube stages. We present evidence that there is an early prepattern for Hoxd10 expression in the lumbosacral neural tube; a prepattern that is established at or before stages of neural tube closure. Cells within more posterior lumbosacral segments have a greater ability to develop high level Hoxd10 expression than the most anterior lumbosacral segments or thoracic segments. During subsequent neural tube stages, this prepattern is amplified and stabilized by environmental signals such that all lumbosacral segments acquire the ability to develop high levels of Hoxd10, independent of their axial environment. Results from experiments in which posterior neural segments and/or paraxial mesoderm segments were placed at different axial levels suggest that signals setting Hoxd10 expression form a decreasing posterior-to-anterior gradient. Our experiments do not, however, implicate adjacent paraxial mesoderm as the only source of graded signals. We suggest, instead, that signals from more posterior embryonic regions influence Hoxd10 expression after the early establishment of a regional prepattern. Concurrent analyses of patterns of LIM proteins and motor column organization after experimental surgeries suggest that the programming of these characteristics follows similar rules. 相似文献
5.
Marshall C Elias C Xue XH Le HD Omelchenko A Hryshko LV Tibbits GF 《American journal of physiology. Cell physiology》2002,283(2):C512-C520
The cardiacNa+/Ca2+ exchanger (NCX) in troutexhibits profoundly lower temperature sensitivity in comparison to themammalian NCX. In this study, we attempt to characterize the regions of the NCX molecule that are responsible for its temperature sensitivity. Chimeric NCX molecules were constructed using wild-type trout andcanine NCX cDNA and expressed in Xenopus oocytes.NCX-mediated currents were measured at 7, 14, and 30°C using thegiant excised-patch technique. By using this approach, the differentialtemperature dependence of NCX was found to reside within theNH2-terminal region of the molecule. Specifically, we foundthat ~75% of the Na+/Ca2+ exchangedifferential energy of activation is attributable to sequencedifferences in the region that include the first four transmembranesegments, and the remainder is attributable to transmembrane segmentfive and the exchanger inhibitory peptide site. 相似文献
6.
Hans-Joachim Wieden Kirill Gromadski Dmytro Rodnin Marina V Rodnina 《The Journal of biological chemistry》2002,277(8):6032-6036
Nucleotide exchange in elongation factor Tu (EF-Tu) is catalyzed by elongation factor Ts (EF-Ts). Similarly to other GTP-binding proteins, the structural changes in the P loop and the Mg(2+) binding site are known to be important for nucleotide release from EF-Tu. In the present paper, we determine the contribution of the contacts between helix D of EF-Tu at the base side of the nucleotide and the N-terminal domain of EF-Ts to the catalysis. The rate constants of the multistep reaction between Escherichia coli EF-Tu, EF-Ts, and GDP were determined by stopped-flow kinetic analysis monitoring the fluorescence of either Trp-184 in EF-Tu or mant-GDP. Mutational analysis shows that contacts between helix D of EF-Tu and the N-terminal domain of EF-Ts are important for both complex formation and the acceleration of GDP dissociation. The kinetic results suggest that the initial contact of EF-Ts with helix D of EF-Tu weakens binding interactions around the guanine base, whereas contacts of EF-Ts with the phosphate binding side that promotes the release of the phosphate moiety of GDP appear to take place later. This "base-side-first" mechanism of guanine nucleotide release resembles that found for Ran x RCC1 and differs from mechanisms described for other GTPase x GEF complexes where interactions at the phosphate side of the nucleotide are released first. 相似文献
7.
The attachment ability of insects on surfaces are associated not only with the micro- and nanostructure of the adhering part
of an attachment device, but also with the global scale kinematics responsible for contact formation and release. In the present
study, the locomotory techniques of several representatives of insects from four different orders (Orthoptera, Heteroptera,
Coleoptera, and Hymenoptera), possessing different types of attachment structures, are described. The study is based on video
recordings of insects walking on a flat surface and on cylindrical rods of various thickness, imitating plant stems. Attachment
devices of tarsi and pretarsi were visualized using Scanning Electron Microscopy. The results show a different manner in the
use of adhesive structures on substrates with various curvatures. Insects bearing attachment pads on proximal tarsomeres usually
touch flat and curved substrates using all tarsomeres, whereas insects with their attachment devices on the distal tarsomeres
usually walk on flat surfaces using the distal tarsomeres of the overextended tarsus. On substrates, with diameters comparable
to or larger than the tarsus length, insects walk above the stem by clasping the stem with the bent tarsi. On thin stems,
insects clasp the stem between their tarsi and hang under the stem. Thus, on thin and thick rods, forces applied to attachment
organs act in opposite directions. There are two methods of leg positioning for walking on a rough flat substrate. In the
first case, the tarsus is straightened and the rough substrate is gripped between the claws and the proximal complex of attachment
devices (tarsal euplantulae, fossulae spongiosa, and terminal spurs of tibiae). In the second case the tibia does not touch
the substrate; the insect is supported only by distal tarsomeres. The tarsus is in an overextended condition. On rods, with
diameters comparable to or larger than the tarsus length, insects walk by clasping the stem with the bent tarsi. This posture
is characteristic for the majority of insects independent of the tarsal position they normally use while walking on a plane.
If the rod’s diameter is smaller than the tarsus length, walking insects usually clutch it between contralateral tarsi. Using
such a posture they are supported by interlocking or by strong friction, generated by attachment devices of the proximal tarsomeres,
and do not use attachment devices of the pretarsus. Contact with the substrate is reinforced due to the coordinated contralateral
clutch using all supporting legs. It is concluded that the use of different types of attachment structures correlates with
locomotory techniques.
Handling Editor: Heikki Hokkanen 相似文献
8.
Background
Graves’ disease (GD) is a common cause of hyperthyroidism resulting in development of thyrotoxic heart disease (THD).Objectives
to assess cardiovascular disorders and health related quality of life (HRQoL) in patients with THD secondary to GD.Patients and Methods
All patients diagnosed with THD secondary to GD between January 2011 and December 2013 were eligible for this study. Clinical assessment was performed at baseline and at the follow-up visit after the restoring of euthyroid state. HRQoL was studied with a questionnaire EQ-5D-5L.Results
Follow-up data were available for 61 patients, but only 30 patients with THD secondary to GD were consented to participate in investigation of their HRQoL. The frequency of cardiovascular complications was significantly reduced as compared before and after the antithyroid therapy as follows: resting heart rate (122 vs. 74 bpm), blood pressure: systolic (155 vs. 123 mm Hg), diastolic (83 vs. 66 mm Hg), supraventricular premature contractions (71% vs. 7%), atrial fibrillation (72% vs. 25%), congestive heart failure (69% vs. 20%), thyrotoxic cardiomyopathy (77% vs. 26%), all p<0.01. Anti-TSH receptor antibodies were determined as independent predictor of left ventricular geometry changes, (b-coefficient = 0.04, 95%CI 0.01–0.07, p = 0.02). HRQoL was improved in all domains and self-rated health increased from 43 to 75 units by visual analogue score (p<0.001).Conclusions
Restoring of euthyroid state in patients with GD is associated with significant elimination of cardiovascular disorders and improvement of HRQoL. To our knowledge this is the first study evaluating Ukrainian patients with THD secondary to GD with focus on HRQoL. 相似文献9.
Dmytro V. Gospodaryov Oleh V. Lushchak Bohdana M. Rovenko Natalia V. Perkhulyn Mike Gerards Tea Tuomela Howard T. Jacobs 《BBA》2014
An assembled cDNA coding for the putative single-subunit NADH dehydrogenase (NDX) of Ciona intestinalis was introduced into Drosophila melanogaster. The encoded protein was found to localize to mitochondria and to confer rotenone-insensitive substrate oxidation in organello. Transgenic flies exhibited increased resistance to menadione, starvation and temperature stress, and manifested a sex and diet-dependent increase in mean lifespan of 20–50%. However, NDX was able only weakly to complement the phenotypes produced by the knockdown of complex I subunits. 相似文献
10.
Synthesis of 6-amino-2-azaspiro[3.3]heptane-6-carboxylic acid and 2-azaspiro[3.3]heptane-6-carboxylic acid was performed.
Both four-membered rings in the spirocyclic scaffold were constructed by subsequent ring closure of corresponding 1,3-bis-electrophiles
at 1,1-C- or 1,1-N-bis-nucleophiles. The two novel amino acids were added to the family of the sterically constrained amino acids for the use
in chemistry, biochemistry, and drug design. 相似文献