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101.
Christian Castro 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):217-232
Binding of the transition state analogue coformycin and the ground state analogue 1-deaazadenosine to bovine adenosine deaminase have been thermody-namically characterized. The heat capacity changes for coformycin and 1-deazaadenosine binding are - 4.7 × 0.8 kJ/mole-K and -1.2 × 0.1 kJ/mole-K, respectively. Since the predominant source of heat capacity change in enzyme interactions are changes in the extent of exposure of nonpolar amino acid side chains to the aqueous environment and the hydrophobic effect is the predominant factor in native structure stabilization, we propose that the binding of either class of ligand is associated with a stabilizing enzyme conformational change with coformycin producing the far greater effect Analysis of the T dependence of the second order rate constant for formation of the enzyme/coformycin complex further reveals that the conformational change is not rate limiting. We propose that the enzyme may facilitate catalysis via the formation of a stabilizing conformation at the reaction transition state. 相似文献
102.
Previous researches mainly focused on the runoff responses to landuse change based on annual, seasonal or monthly time scales, there are few studies based on daily scale. We conducted a comprehensive investigation into runoff responses on the daily scale as well as annual and monthly time scales using SWAT, and compared the impacts of time scales with different time indicators quantitatively. Jinjiang, a coastal catchment of southeast China with a humid sub-tropical climate, was used for simulations. A calibrated SWAT model produced satisfactory reproduction of annual, monthly and daily runoff processes over a nine-year (2002–2010) period at three gauging stations. Runoff was then simulated and compared using the same meteorological input but two different landuse scenarios (1985 and 2006, with reduced forest and increased cropland and urbanized area). The results showed varying change in runoff among three time scales and three catchments. The annual runoff had the smallest increase between two scenarios, monthly runoffs had medium rates (increasing in all months except October–November), and daily runoff had the largest rates with the increase in flood peaks but decrease in drought flows, because of the variable influence on interception/evapotranspiration loss, percolation and antecedent soil water storage. Indicators of different time scales (annual runoff, monthly runoff, maximum 1-day and 5-day flood runoff, minimum 1-day and 7-day runoff) proved appropriate for analysing landuse change impacts. 相似文献
103.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):1363-1365
Abstract The initial experiments towards the chemical synthesis of conformationally rigid peptide nucleic acid analogues with azetidine moieties have been described. 相似文献
104.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):723-725
Abstract Ring-closing metathesis (RCM) is applied as a new and powerful technology in the construction of nucleoside analogues that are conformationally restricted in S-type conformations due to additional 3′,4′- and/or 3′,5′-linkages. 相似文献
105.
Jennifer L. Powers R. Richard Plaskon Greta A. Olsen Sheldon W. May 《Journal of neurochemistry》1995,65(5):2031-2042
Abstract: The adrenal medullary chromaffin cell is a commonly used model for the adrenergic neuron. Although much work has been done to study the transport system in the adrenal chromaffin vesicles, relatively little is known about cellular transport, especially with regard to structural features of phenethylamines required for intracellular accumulation. We have now investigated the structural requirements of phenethylamine-related compounds for their accumulation into cultured adrenal chromaffin cells. We find that two types of cellular uptake, previously described only for dopamine, norepinephrine, and epinephrine, are also present for [3H]tyramine. Although two types of accumulation occur, tyramine accumulation occurs mainly via a cocaine-insensitive process, whereas dopamine accumulation occurs predominantly via a cocaine-sensitive process. The accumulation of [14C]-phenethylamine and p-methoxyphenethylamine is not affected by cocaine, suggesting that a ring hydroxyl substituent is necessary for cocaine-sensitive accumulation. The compounds p-hydroxyphenylpropylamine and p-hydroxyphenyl-2-aminoethyl sulfide accumulate in the cell only via a cocaine-insensitive process, indicating that lengthening of the aminoalkyl side chain prevents cocaine-sensitive accumulation. We have performed conformational analyses of this series of compounds to determine whether the conformation of these compounds can be related to the kinetic data. For dopamine, tyramine, phenethylamine, and p-methoxyphenethylamine, two groups of energy-minimized conformers were found. We find that there is an approximately linear relationship between the Km values for these phenethylamines and the differences in minimized energies between the low- and highest energy conformer groups of each compound. A similar correlation was found for p-hydroxyphenyl-2-aminoethyl sulfide. These results are consistent with the hypothesis that these compounds undergo a conformational change from the low-energy conformer to the highest energy conformer before their cocaine-insensitive accumulation. 相似文献
106.
Teppei Ikeya David Ban Donghan Lee Yutaka Ito Koichi Kato Christian Griesinger 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(2):287-306
Background
To understand the mechanisms related to the ‘dynamical ordering’ of macromolecules and biological systems, it is crucial to monitor, in detail, molecular interactions and their dynamics across multiple timescales. Solution nuclear magnetic resonance (NMR) spectroscopy is an ideal tool that can investigate biophysical events at the atomic level, in near-physiological buffer solutions, or even inside cells.Scope of review
In the past several decades, progress in solution NMR has significantly contributed to the elucidation of three-dimensional structures, the understanding of conformational motions, and the underlying thermodynamic and kinetic properties of biomacromolecules. This review discusses recent methodological development of NMR, their applications and some of the remaining challenges.Major conclusions
Although a major drawback of NMR is its difficulty in studying the dynamical ordering of larger biomolecular systems, current technologies have achieved considerable success in the structural analysis of substantially large proteins and biomolecular complexes over 1 MDa and have characterised a wide range of timescales across which biomolecular motion exists. While NMR is well suited to obtain local structure information in detail, it contributes valuable and unique information within hybrid approaches that combine complementary methodologies, including solution scattering and microscopic techniques.General significance
For living systems, the dynamic assembly and disassembly of macromolecular complexes is of utmost importance for cellular homeostasis and, if dysregulated, implied in human disease. It is thus instructive for the advancement of the study of the dynamical ordering to discuss the potential possibilities of solution NMR spectroscopy and its applications. This article is part of a Special Issue entitled “Biophysical Exploration of Dynamical Ordering of Biomolecular Systems” edited by Dr. Koichi Kato. 相似文献107.
《Cell calcium》2018
A novel pathway of methylglyoxal (MGX)-induced apoptosis via sarcoplasmic reticulum Ca2+-ATPase (SERCA) is presented. Interaction of SERCA1 with MGX was investigated by molecular docking and experimentally in a cell-free system. MGX concentration- and time-dependently decreased SERCA1 activity. A significant increase of sarcoplasmic reticulum (SR) carbonylation was found in the concentration range of 1–10 mM caused by MGX and a decrease of thiol groups at the concentrations of 5 and 40 mM. Affinities of SERCA1 to ATP and Ca2+ were not influenced by MGX, however decreases of Vmax related to both binding sites were observed. Molecular docking indicated binding of MGX at the cytosolic region of SERCA1, inducing conformational changes in the cytosolic-transmembrane interface. This interaction resulted in conformational changes in the cytosolic region (FITC fluorescence decrease) as well as in the transmembrane region of SERCA1 (Trp fluorescence decrease) without direct binding to the cytosolic ATP or transmembrane Ca2+ binding sites.Regarding the MGX inhibitory effect in a cell-free system and similarities of SERCA1 to its other isoforms, proapoptotic properties of MGX may be expected in cellular systems. At cellular level, MGX induced a decrease of SERCA2b expression in the pancreatic INS-1E β-cell line. This was accompanied by cell viability decrease, increase in apoptosis, impaired insulin secretion and elevation of basal intracellular Ca2+ levels. Decreased expression of SERCA2b may contribute to induction of apoptosis of pancreatic β-cells. 相似文献
108.
Zhang LQ Zhang HJ Guo P Xue P Xie ZS Chen Z Jing GZ 《Archives of biochemistry and biophysics》2007,466(2):211-220
The in vivo activities and conformational changes of ribosome recycling factor from Thermoanaerobacter tengcongensis (TteRRF) with 12 successive C-terminal deletions were compared. The results showed that TteRRF mutants lacking one to four amino acid residues are inactive, those lacking five to nine are reactivated to a similar or a little higher level than wild-type TteRRF, and those lacking ten to twelve are inactivated again gradually. Conformational studies indicated that only the ANS binding fluorescence change is correlated well with the RRF in vivo activity change, while the secondary structure and local structure at the aromatic residues are not changed significantly. Trypsin cleavage site identification and protein stability measurement suggested that mutation only induced subtle conformation change and increased flexibility of the protein. Our results indicated that the ANS-detected local conformation changes of TteRRF and mutants are one verified direct reason of the in vivo inactivation and reactivation in Escherichia coli. 相似文献
109.
Scrima M Campiglia P Esposito C Gomez-Monterrey I Novellino E D'Ursi AM 《Biochemical and biophysical research communications》2007,363(3):500-505
Obestatin and its derivative Ob(11-23) are recently discovered peptides produced in the rat stomach. They have proven to be involved in the regulation of energy balance, inhibiting feeding, causing reductions in food intake, body weight and jejunal contraction in rodents. The G-protein coupled receptor, GPR39, was originally proposed as being an obestatin target receptor, but this remains controversial. As such, the molecular mechanism for obestatin's effects in vivo is still uncertain. Here we report the CD and NMR conformational analysis of obestatin and Ob(11-23). Both peptides assume a regular secondary structure in the C-terminal region of the molecule. In this region, structural elements similar to other GPCR binding neuropeptides support the identity of obestatin as a new and functionally autonomous GPCR ligand. Conversely sequence and conformational specificity point to a new farmacoforic structure, on which innovative derivatives with a potential role in the treatment of obesity can be designed and synthetized. 相似文献
110.
Murray Goodman Ralph-Heiko Mattern Peter Gantzel Antonello Santini Rosa Iacovino Michele Saviano Ettore Benedetti 《Journal of peptide science》1998,4(4):229-238
The molecular basis of sweet taste was investigated by carrying out the crystal state conformational analysis by X-ray diffraction of the following dipeptide taste igands:N-3,3-dimethylbutyl-aspartyl-phenylalanine methyl ester, I (N-DMB-Asp-Phe-OMe), its sodium salt (N-DMB-Asp-Phe-ONa), II , aspartyl-D -2-aminobutyric acid-(S)-α-ethylbenzylamide, III (Asp-D -Abu-(S)-α-ethylbenzylamide), aspartyl-N′-((2,2,5,5-tetramethylcyclopentanyl)-carbonyl)-(R)-1,1-diamino-ethane, IV (Asp-(R)-gAla-TMCP), and aspartyl-D -valine-(R)-α-methoxymethylbenzyl amide, V (Asp-D -Val-(R)-α-methoxymethylbenzylamide). With the exception of the sodium salt II , all compounds are sweet-tasting, showing in some cases considerable potency enhancement with respect to sucrose. The results of this study confirm the earlier model that an ‘L-shape’ molecular array is essential for eliciting sweet taste for dipeptide-like ligands. In addition, it was established that (i) substitution of the N-terminal group does not inhibit sweet taste, if its zwitterionic character is maintained; (ii) a hydrophobic group located between the stem and the base of the L-shape could be responsible for sweetness potency enhancement, as found in I, III and IV ; in fact, the extraordinary potency of the N-alkylated analogue I would support a model with an additional hydrophobic binding domain above the base of the ‘L’; (iii) removal of the methyl ester at the C-terminus of compound I with the salt formation gives rise to the tasteless compound II ; (iv) for the first time all possible side-chain conformers (g−,g+andt) for the N-substituted aspartyl residue were observed; and (v) a retro-inverso modification, incorporated at position 2 of the dipeptide chain, confers greater flexibility to the molecule, as demonstrated by the contemporary presence of six conformationally distinct independent molecules in the unit cell and yet sweet taste properties are maintained, as found in IV . © 1998 European Peptide Society and John Wiley & Sons, Ltd. 相似文献