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排序方式: 共有433条查询结果,搜索用时 31 毫秒
21.
Shabana Vohra Bruck Taddese Alex C. Conner David R. Poyner Debbie L. Hay James Barwell Philip J. Reeves Graham J. G. Upton Christopher A. Reynolds 《Journal of the Royal Society Interface》2013,10(79)
Modelling class B G-protein-coupled receptors (GPCRs) using class A GPCR structural templates is difficult due to lack of homology. The plant GPCR, GCR1, has homology to both class A and class B GPCRs. We have used this to generate a class A–class B alignment, and by incorporating maximum lagged correlation of entropy and hydrophobicity into a consensus score, we have been able to align receptor transmembrane regions. We have applied this analysis to generate active and inactive homology models of the class B calcitonin gene-related peptide (CGRP) receptor, and have supported it with site-directed mutagenesis data using 122 CGRP receptor residues and 144 published mutagenesis results on other class B GPCRs. The variation of sequence variability with structure, the analysis of polarity violations, the alignment of group-conserved residues and the mutagenesis results at 27 key positions were particularly informative in distinguishing between the proposed and plausible alternative alignments. Furthermore, we have been able to associate the key molecular features of the class B GPCR signalling machinery with their class A counterparts for the first time. These include the [K/R]KLH motif in intracellular loop 1, [I/L]xxxL and KxxK at the intracellular end of TM5 and TM6, the NPXXY/VAVLY motif on TM7 and small group-conserved residues in TM1, TM2, TM3 and TM7. The equivalent of the class A DRY motif is proposed to involve Arg2.39, His2.43 and Glu3.46, which makes a polar lock with T6.37. These alignments and models provide useful tools for understanding class B GPCR function. 相似文献
22.
Catledge SA Fries MD Vohra YK Lacefield WR Lemons JE Woodard S Venugopalan R 《Journal of nanoscience and nanotechnology》2002,2(3-4):293-312
Recent progress in the synthesis, characterization, and biological compatibility of nanostructured ceramics for biomedical implants is reviewed. A major goal is to develop ceramic coating technology that can reduce the friction and wear in mating total joint replacement components, thus contributing to their significantly improved function and longer life span. Particular attention is focused on the enhancement of mechanical properties such as hardness, toughness, and friction coefficient and on the bioactivity as they pertain to the nanostructure of the material. The development of three nanostructured implant coatings is discussed: diamond, hydroxyapatite, and functionally graded metalloceramics based on the Cr-Ti-N ternary system. Nanostructured diamond produced by chemical vapor deposition (CVD) techniques and composed of nano-size diamond grains have particular promise because of the combination of ultrahigh hardness, improved toughness over conventional microcrystalline diamond, low friction, and good adhesion to titanium alloys. Nanostructured processing applied to hydroxyapatite coatings is used to achieve the desired mechanical characteristics and enhanced surface reactivity and has been found to increase osteoblast adhesion, proliferation, and mineralization. Finally, nanostructured metalloceramic coatings provide continuous variation from a nanocrystalline metallic bond at the interface to the hard ceramic bond on the surface and have the ability to overcome adhesion problems associated with ceramic hard coatings on metallic substrates. 相似文献
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Administration (p.o.) of SKP-450, 2-[2"-(1",3"-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro-2H- 1-benzopyran, a novel antihypertensive agent, to hypercholesterolemic Syrian hamsters led to a significant reduction in plasma lipids in a dose-dependent manner, i.e., a 10.8% to 29% reduction in low-density lipoprotein cholesterol at doses of 0.3 to 10 mg/kg of SKP-450. SKP-450 was found to specifically inhibit the hepatic microsomal lanosterol 14alpha-methyl demethylase (14alpha-DM) in a competitive manner (Ki:2.65 microM). Furthermore, a dose-dependent decrease in the 14alpha-DM activity by SKP-450 parallelled the cholesterol synthetic rate in vitro in both the rat hepatic S10 fractions (supernatants at 10,000 g; IC50:20 microM) and Chinese hamster ovary cells (IC50:23 microM). However, this phenomenon was not seen in AR45 cells, which are deficient in 14alpha-DM, suggesting that 14alpha-DM is the major target for the inhibitory action of SKP-450 in regard to cholesterol biosynthesis. 相似文献
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Many biomolecules are characterized by surfaces containing extended nonpolar regions, and the aggregation and subsequent removal of such surfaces from water is believed to play a critical role in the biomolecular assembly in cells. A better understanding of the hydrophobic hydration of biomolecules may therefore yield new insights into intracellular assembly. Conventional views hold that the hydration shell of small hydrophobic solutes is clathrate-like, characterized by local cage-like hydrogen-bonding structures and a distinct loss in entropy. The hydration of extended nonpolar planar surfaces, however, appears to involve structures that are orientationally inverted relative to clathrate-like hydration shells, with unsatisfied hydrogen bonds that are directed towards the hydrophobic surface. Here we present computer simulations of the interaction between the polypeptide melittin and water that demonstrate that the two different hydration structures also exist near a biomolecular surface. We find that the two structures are distinguished by a substantial difference in the water-water interaction enthalpy, and that their relative contributions depend strongly on the surface topography of the melittin molecule: clathrate-like structures dominate near convex surface patches, whereas the hydration shell near flat surfaces fluctuates between clathrate-like and less-ordered or inverted structures. The strong influence of surface topography on the structure and free energy of hydrophobic hydration is likely to hold in general, and will be particularly important for the many biomolecules whose surfaces contain convex patches, deep or shallow concave grooves and roughly planar areas. 相似文献
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The rate of nitrosation of dihexylamine is enhanced when the reaction is carried ut in the presence of micelles containing bile acid conjugates or bile acid conjugates and lecithin. The nitrosation of smaller dialkylamines is not affected. The nitrosation of dihexylamine under these conditions is inhibited by alpha-tocopherol at pH 3 or pH 5. At pH 3 the reaction is inhibited by ascorbic acid, while at pH 5 it is inhibited by equimolar concentrations of ascorbic acid, but accelerated by higher concentration of ascorbic acid. The effect of ascorbic acid at pH 5 depends on the presence of oxygen and sulfamate. 相似文献
30.
Papo MJ Catledge SA Vohra YK Machado C 《Journal of materials science. Materials in medicine》2004,15(7):773-777
We used microwave plasma chemical vapor deposition to deposit nanocrystalline and multilayer (nanocrystalline/microcrystalline/nanocrystalline) diamond thin films on Ti-6AI-4V substrates imitating the condyle and fossa components of the temporomandibular joint. We tested the condyle/fossa pairs for wear in a mandibular movement simulator for an equivalent of two years of clinical use. Analysis of the wear surfaces by optical microscopy, scanning electron microscopy (SEM), and Raman spectroscopy showed that damage in both the films was minimal, no loss of film occurred and the wear performance was superior for the multilayer film. Comparisons with an uncoated condyle/fossa pair showed that the coated temporomandibular joint pairs had improved wear performance. 相似文献