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71.
介绍了X射线衍射技术在研究蛋白质动态过程中的应用.首先介绍了用常规X射线衍射法和劳埃X射线衍射法等数据采样法研究反应时间为几分钟的蛋白质催化反应.然后介绍了通过选择不匹配底物,不适宜酸度,选择温度和酸度的跳跃,金属和光化学瞬时激发达到反应的同步来研究反应时间为几秒钟的蛋白质催化反应. 相似文献
72.
The role of ceramide chain length distribution on the barrier properties of the skin lipid membranes
The skin barrier function is provided by the stratum corneum (SC). The lipids in the SC are composed of three lipid classes: ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs) which form two crystalline lamellar structures. In the present study, we investigate the effect of CER chain length distribution on the barrier properties of model lipid membranes mimicking the lipid composition and organization of SC. The membranes were prepared with either isolated pig CERs (PCERs) or synthetic CERs. While PCERs have a wide chain length distribution, the synthetic CERs are quite uniform in chain length. The barrier properties were examined by means of permeation studies using hydrocortisone as a model drug. Our studies revealed a reduced barrier in lipid membranes prepared with PCERs compared to synthetic CERs. Additional studies revealed that a wider chain length distribution of PCERs results in an enhanced hexagonal packing and increased conformational disordering of the lipid tails compared to synthetic CERs, while the lamellar phases did not change. This demonstrates that the chain length distribution affects the lipid barrier by reducing the lipid ordering and density within the lipid lamellae. In subsequent studies, the effect of increased levels of FFAs or CERs with a long acyl chain in the PCERs membranes was also studied. These changes in lipid composition enhanced the level of orthorhombic packing, reduced the conformational disordering and increased the barrier of the lipid membranes. In conclusion, the CER chain length distribution is an important key factor for maintaining a proper barrier. 相似文献
73.
Beate-Annette Brüning Sylvain Prévost Ralf Stehle Roland Steitz Peter Falus Bela Farago Thomas Hellweg 《生物化学与生物物理学报:生物膜》2014
We report a combined dynamic light scattering (DLS) and neutron spin-echo (NSE) study on the local bilayer undulation dynamics of phospholipid vesicles composed of 1,2-dimyristoyl-glycero-3-phosphatidylcholine (DMPC) under the influence of temperature and the additives cholesterol and trehalose. The additives affect vesicle size and self-diffusion. Mechanical properties of the membrane and corresponding bilayer undulations are tuned by changing lipid headgroup or acyl chain properties through temperature or composition. On the local length scale, changes at the lipid headgroup influence the bilayer bending rigidity κ less than changes at the lipid acyl chain: We observe a bilayer softening around the main phase transition temperature Tm of the single lipid system, and stiffening when more cholesterol is added, in concordance with literature. Surprisingly, no effect on the mechanical properties of the vesicles is observed upon the addition of trehalose. 相似文献
74.
Background
The concentration of iron in the brain increases with aging. Furthermore, it has also been observed that patients suffering from neurological diseases (e.g. Parkinson, Alzheimer…) accumulate iron in the brain regions affected by the disease. Nevertheless, it is still not clear whether this accumulation is the initial cause or a secondary consequence of the disease. Free iron excess may be an oxidative stress source causing cell damage if it is not correctly stored in ferritin cores as a ferric iron oxide redox-inert form.Scope
Both, the composition of ferritin cores and their location at subcellular level have been studied using analytical transmission electron microscopy in brain tissues from progressive supranuclear palsy (PSP) and Alzheimer disease (AD) patients.Major conclusions
Ferritin has been mainly found in oligodendrocytes and in dystrophic myelinated axons from the neuropili in AD. In relation to the biomineralization of iron inside the ferritin shell, several different crystalline structures have been observed in the study of physiological and pathological ferritin. Two cubic mixed ferric–ferrous iron oxides are the major components of pathological ferritins whereas ferrihydrite, a hexagonal ferric iron oxide, is the major component of physiological ferritin. We hypothesize a dysfunction of ferritin in its ferroxidase activity.General significance
The different mineralization of iron inside ferritin may be related to oxidative stress in olygodendrocites, which could affect myelination processes with the consequent perturbation of information transference. 相似文献75.
The preparation of new palladium(II) and platinum(II) complexes derived from alpha-diphenyl ethanedione bis(thiosemicarbazone), 1, and alpha-diphenyl ethanedione bis(4-ethylthiosemicarbazone), 2, is described. The palladium complexes 3 and 4 and platinum complexes 5 and 6 have been characterized by elemental analyses, fast atom bombardment mass spectrometry (FAB(+)) and spectroscopic studies (IR, (1)HNMR). The crystal and molecular structures of the dimeric cyclopalladated compound 4 and the mononuclear platinum complex 6 have been determined by single crystal X-ray diffraction. The cytotoxic activity of the free ligands and palladium and platinum complexes against human A2780 and A2780cisR (acquired resistance to cisplatin) epithelial ovarian carcinoma cells lines is also reported. The IC(50) values for compounds 1, 5 and 6 were found to be higher than that of cisplatin but the maximum antiproliferative activity was similar. Furthermore, the compounds largely retain their activity in the A2780cisR cell line, having a much better resistance factor than cisplatin in the pair of cell lines tested. 相似文献
76.
Oshima K Takezawa Y Sugimoto Y Kobayashi T Irving TC Wakabayashi K 《Journal of molecular biology》2007,367(1):275-301
X-ray diffraction patterns from live vertebrate striated muscles were analyzed to elucidate the detailed structural models of the myosin crown arrangement and the axial disposition of two-headed myosin crossbridges along the thick filaments in the relaxed and contracting states. The modeling studies were based upon the previous notion that individual myosin filaments had a mixed structure with two regions, a "regular" and a "perturbed". In the relaxed state the distributions and sizes of the regular and perturbed regions on myosin filaments, each having its own axial periodicity for the arrangement of crossbridge crowns within the basic period, were similar to those reported previously. A new finding was that in the contracting state, this mixed structure was maintained but the length of each region, the periodicities of the crowns and the axial disposition of two heads of a crossbridge were altered. The perturbed regions of the crossbridge repeat shifted towards the Z-bands in the sarcomere without changing the lengths found in the relaxed state, but in which the intervals between three successive crowns within the basic period became closer to the regular 14.5-nm repeat in the contracting state. In high resolution modeling for a myosin head, the two heads of a crossbridge were axially tilted in opposite directions along the three-fold helical tracks of myosin filaments and their axial orientations were different from each other in perturbed and regular regions in both states. Under relaxing conditions, one head of a double-headed crossbridge pair appeared to be in close proximity to another head in a pair at the adjacent crown level in the axial direction in the regular region. In the perturbed region this contact between heads occurred only on the narrower inter-crown levels. During contraction, one head of a crossbridge oriented more perpendicular to the fiber axis and the partner head flared axially. Several factors that significantly influence the intensities of the myosin based-meridional reflections and their relative contributions are discussed. 相似文献
77.
The crystal structure of mouse Exo70 reveals unique features of the mammalian exocyst 总被引:6,自引:0,他引:6
The exocyst is a eukaryotic tethering complex necessary for the fusion of exocytic vesicles with the plasma membrane. Its function in vivo is tightly regulated by interactions with multiple small GTPases. Exo70, one of the eight subunits of the exocyst, is important for the localization of the exocyst to the plasma membrane. It interacts with TC10 and Rho3 GTPases in mammals and yeast, respectively, and has been shown recently to bind to the actin-polymerization complex Arp2/3. Here, we present the crystal structure of Mus musculus Exo70 at 2.25 A resolution. Exo70 is composed of alpha-helices in a series of right-handed helix-turn-helix motifs organized into a long rod of length 170 A and width 35 A. Although the alpha-helical organization of this molecule is similar to that in Saccharomyces cerevisiae Exo70, major structural differences are observed on the surface of the molecule, at the domain boundaries, and in various loop structures. In particular, the C-terminal domain of M. musculus Exo70 adopts a new orientation relative to the N-terminal half not seen in S. cerevisiae Exo70 structures. Given the low level of sequence conservation within Exo70, this structure provides new insights into our understanding of many species-specific functions of the exocyst. 相似文献
78.
Burk DL Hwang J Kwok E Marrone L Goodfellow V Dmitrienko GI Berghuis AM 《Journal of molecular biology》2007,373(3):745-754
The 1.64 A structure of the apoenzyme form of saccharopine dehydrogenase (SDH) from Saccharomyces cerevisiae shows the enzyme to be composed of two domains with similar dinucleotide binding folds with a deep cleft at the interface. The structure reveals homology to alanine dehydrogenase, despite low primary sequence similarity. A model of the ternary complex of SDH, NAD, and saccharopine identifies residues Lys77 and Glu122 as potentially important for substrate binding and/or catalysis, consistent with a proton shuttle mechanism. Furthermore, the model suggests that a conformational change is required for catalysis and that residues Lys99 and Asp281 may be instrumental in mediating this change. Analysis of the crystal structure in the context of other homologous enzymes from pathogenic fungi and human sources sheds light into the suitability of SDH as a target for antimicrobial drug development. 相似文献
79.
A new series of chiral carboxylate-bridged complexes of Mn(II), Co(II), and Ni(II) has been synthesized by reaction of M(II) salts with (S)-2-hydroxy-2-methyl-butanedioic acid ((S)-citramalic acid) under solvothermal conditions. The Mn(II) compound 1 is obtained as a crystalline powder, whereas the Co(II) and Ni(II) compounds (2 and 3 respectively) are obtained as single crystals. All the compounds crystallize in orthorhombic chiral space group P212121. Compounds 2 and 3 are isostructural, and their structure consists in helicoïdal chains of M(II) centres linked by carboxylate bridges. The magnetic data indicate a rather weak coupling interaction between paramagnetic centres. The Mn(II) compound 1 exhibits antiferromagnetic ordering at TN = 2.64 K. The Co(II) and Ni(II) compounds show ferromagnetic interactions within the chains. For 3, the chains couple antiferromagnetically, which leads to a metamagnetic behaviour with TN = 1.69 K. 相似文献
80.
Tobias Rüffer Björn Bräuer Bernhard Walfort Annie K. Powell Lorenzo Sorace 《Inorganica chimica acta》2007,360(12):3777-3784
The new mononuclear bis(oxamato) complex [n-Bu4N]2[Cu(obbo)] (1) (obbo=o-benzyl-bis(oxamato)) has been synthesized as a precursor for trinuclear oxamato-bridged transition metal complexes. Starting from 1 the homotrinuclear complexes [Cu3(obbo)(pmdta)2(NO3)](NO3)·CH2Cl2·H2O (2) and [Cu3(obbo)(tmeda)2(NO3)2(dmf)] (3) have been prepared, where pmdta = N,N,N′,N″,N″-pentamethyldiethylenetriamine, tmeda = N,N,N′,N′-tetramethylethylenediamine and dmf = dimethylformamide. The crystal structures of 1-3 were solved. The magnetic properties of 2 and 3 were studied by susceptibility measurements versus temperature. For the intramolecular J parameter values of −111 cm−1 (2) and −363 cm−1 (3) were obtained. 相似文献