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281.
Niimura N Arai S Kurihara K Chatake T Tanaka I Bau R 《Cellular and molecular life sciences : CMLS》2006,63(3):285-300
Neutron diffraction provides an experimental method of directly locating hydrogen atoms in proteins, a technique complimentary to ultra-high-resolution [1, 2] X-ray diffraction. Three different types of neutron diffractometers for biological macromolecules have been constructed in Japan, France and the United States, and they have been used to determine the crystal structures of proteins up to resolution limits of 1.5-2.5 A. Results relating to hydrogen positions and hydration patterns in proteins have been obtained from these studies. Examples include the geometrical details of hydrogen bonds, H/D exchange in proteins and oligonucleotides, the role of hydrogen atoms in enzymatic activity and thermostability, and the dynamical behavior of hydration structures, all of which have been extracted from these structural results and reviewed. Other techniques, such as the growth of large single crystals, the preparation of fully deuterated proteins, the use of cryogenic techniques, and a data base of hydrogen and hydration in proteins, will be described. 相似文献
282.
Snake envenomation is a socio-medical problem of considerable magnitude. About 2.5 million people are bitten by snakes annually,
more than 100,000 fatally. However, although bites can be deadly, snake venom is a natural biological resource that contains
several components of potential therapeutic value. Venom has been used in the treatment of a variety of pathophysiological
conditions in Ayurveda, homeopathy and folk medicine. With the advent of biotechnology, the efficacy of such treatments has
been substantiated by purifying components of venom and delineating their therapeutic properties. This review will focus on
certain snake venom components and their applications in health and disease.
Received 6 July 2006; received after revision 14 August 2006; accepted 28 September 2006 相似文献
283.
Pahan K 《Cellular and molecular life sciences : CMLS》2006,63(10):1165-1178
Although a change in life-style is often the method of first choice for lipid lowering, lipid-lowering drugs, in general,
help to control elevated levels of different forms of lipids in patients with hyperlipidemia. While one group of drugs, statins,
lowers cholesterol, the other group, fibrates, is known to take care of fatty acids and triglycerides. In addition, other
drugs, such as ezetimibe, colesevelam, torcetrapib, avasimibe, implitapide, and niacin are also being considered to manage
hyperlipidemia. As lipids are very critical for cardiovascular diseases, these drugs reduce fatal and nonfatal cardiovascular
abnormalities in the general population. However, a number of recent studies indicate that apart from their lipidlowering
activities, statins and fibrates exhibit multiple functions to modulate intracellular signaling pathways, inhibit inflammation,
suppress the production of reactive oxygen species, and modulate T cell activity. Therefore, nowadays, these drugs are being
considered as possible therapeutics for several forms of human disorders including cancer, autoimmunity, inflammation, and
neurodegeneration. Here I discuss these applications in the light of newly discovered modes of action of these drugs.
Received 5 September 2005; received after revision 29 December 2005; accepted 26 January 2006 相似文献
284.
285.
DNA methylation profiling of human chromosomes 6, 20 and 22 总被引:24,自引:0,他引:24
286.
Kertész A Váradi G Tóth GK Fajka-Boja R Monostori E Sármay G 《Cellular and molecular life sciences : CMLS》2006,63(22):2682-2693
Phosphopeptides interacting with src homology 2 (SH2) domains can activate essential signaling enzymes in vitro. When delivered to cells, they may disrupt protein-protein interactions, thereby influencing intracellular signaling. We
showed earlier that phosphopeptides corresponding to the inhibitory motif of Fcγ receptor IIb and a motif of the Grb2-associated
binder 1 adaptor protein activate SH2-containing tyrosine phosphatase 2 in vitro. To study the ex vivo effects of these peptides, we have now compared different methods for peptide delivery: (i) permeabilization of the target
cells and (ii) the use of cell-permeable vectors, which are potentially able to transport biologically active compounds into
B cells. We found octanoyl-Arg8 to be an optimal carrier for the delivery of phosphopeptides to the cells. With this strategy, the function of cell-permeable
SHP-2-binding phosphopeptides was analyzed. These peptides modulated the protein phosphorylation in B cells in a dose- and
time-dependent manner.
Received 27 July 2006; received after revision 4 September 2006; accepted 18 September 2006 相似文献
287.
Blasig IE Winkler L Lassowski B Mueller SL Zuleger N Krause E Krause G Gast K Kolbe M Piontek J 《Cellular and molecular life sciences : CMLS》2006,63(4):505-514
Tight junctions seal intercellular clefts via membrane-related strands, hence, maintaining important organ functions. We investigated
the self-association of strand-forming transmembrane tight junction proteins. The regulatory tight junction protein occludin
was differently tagged and cotransfected in eucaryotic cells. These occludins colocalized within the plasma membrane of the
same cell, coprecipitated and exhibited fluorescence resonance energy transfer. Differently tagged strand-forming claudin-5
also colocalized in the plasma membrane of the same cell and showed fluorescence resonance energy transfer. This demonstrates
self-association in intact cells both of occludin and claudin-5 in one plasma membrane. In search of dimerizing regions of
occludin, dimerization of its cytosolic C-terminal coiledcoil domain was identified. In claudin-5, the second extracellular
loop was detected as a dimer. Since the transmembrane junctional adhesion molecule also is known to dimerize, the assumption
that homodimerization of transmembrane tight junction proteins may serve as a common structural feature in tight junction
assembly is supported.
Received 6 October 2005; received after revision 14 December 2005; accepted 27 December 2005
†These authors contributed equally to this work. 相似文献
288.
Anti-amyloidogenic therapies: strategies for prevention and treatment of Alzheimer’s disease 总被引:1,自引:1,他引:0
Deposition of amyloid β-protein (Aβ) in the brain is an early and invariant neuropathological feature of Alzheimer’s disease
(AD). The current search for anti-AD drugs is mainly focused on modification of the process of accumulation of Aβ in the brain.
Here, we review four anti-amyloidogenic strategies: (i) reduction of Aβ production, which has mainly been approached with
secretase inhibition, (ii) promotion of the Aβ degrading catabolic pathway, including an Aβ degrading enzyme, neprilysin,
(iii) immunotherapy for Aβ and (iv) inhibition of Aβ aggregation. We have reported that AD patients have a favorable molecular
environment for Aβ aggregation and that various compounds, such as polyphenols, interfere with Aβ aggregation and destabilize
preformed Aβ fibrils.
Received 21 December 2005; received after revision 14 February 2006; accepted 29 March 2006 相似文献
289.
290.
Early changes of cyclic nucleotide levels in a mitogenic reaction in the rat mesentery. 总被引:2,自引:0,他引:2
By measuring simultaneously cAMP and cGMP we found a biphasic time course with regard to cGMP and the cGMP/cAMP ratio very early in a mitogenic reaction in vivo. This is a new finding. 相似文献