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821.
We develop a coarse-grained protein model with a simplified amino acid interaction potential. Using this model, we perform discrete molecular dynamics folding simulations of a small 20-residue protein--Trp-cage--from a fully extended conformation. We demonstrate the ability of the Trp-cage model to consistently reach conformations within 2-angstroms backbone root-mean-square distance from the corresponding NMR structures. The minimum root-mean-square distance of Trp-cage conformations in simulations can be <1 angstroms. Our findings suggest that, at least in the case of Trp-cage, a detailed all-atom protein model with a molecular mechanics force field is not necessary to reach the native state of a protein. Our results also suggest that the success of folding Trp-cage in our simulations and in the reported all-atom molecular mechanics simulation studies may be mainly due to the special stabilizing features specific to this miniprotein. 相似文献
822.
Shpilyov AV Zinchenko VV Shestakov SV Grimm B Lokstein H 《Biochimica et biophysica acta》2005,1706(3):195-203
Geranylgeranyl reductase catalyses the reduction of geranylgeranyl pyrophosphate to phytyl pyrophosphate required for synthesis of chlorophylls, phylloquinone and tocopherols. The gene chlP (ORF sll1091) encoding the enzyme has been inactivated in the cyanobacterium Synechocystis sp. PCC 6803. The resulting DeltachlP mutant accumulates exclusively geranylgeranylated chlorophyll a instead of its phytylated analogue as well as low amounts of alpha-tocotrienol instead of alpha-tocopherol. Whereas the contents of chlorophyll and total carotenoids are decreased, abundance of phycobilisomes is increased in DeltachlP cells. The mutant assembles functional photosystems I and II as judged from 77 K fluorescence and electron transport measurements. However, the mutant is unable to grow photoautotrophically due to instability and rapid degradation of the photosystems in the absence of added glucose. We suggest that instability of the photosystems in DeltachlP is directly related to accumulation of geranylgeranylated chlorophyll a. Increased rigidity of the chlorophyll isoprenoid tail moiety due to three additional CC bonds is the likely cause of photooxidative stress and reduced stability of photosynthetic pigment-protein complexes assembled with geranylgeranylated chlorophyll a in the DeltachlP mutant. 相似文献
823.
Panov A Dikalov S Shalbuyeva N Taylor G Sherer T Greenamyre JT 《The Journal of biological chemistry》2005,280(51):42026-42035
Chronic infusion of rotenone (Rot) to Lewis rats reproduces many features of Parkinson disease. Rot (3 mg/kg/day) was infused subcutaneously to male Lewis rats for 6 days using Alzet minipumps. Control rats received the vehicle only. Presence of 0.1% bovine serum albumin during the isolation procedure completely removed rotenone bound to the mitochondria. Therefore all functional changes observed were aftereffects of rotenone toxicity in vivo. In Rot rat brain mitochondria (Rot-RBM) there was a 30-40% inhibition of respiration in State 3 and State 3U with Complex I (Co-I) substrates and succinate. Rot did not affect the State 4Deltapsi of RBM and rat liver mitochondria (RLM). However, Rot-RBM required two times less Ca2+ to initiate permeability transition (mPT). There was a 2-fold increase in O*2- or H2O2 generation in Rot-RBM oxidizing glutamate. Rot infusion affected RLM little. Our results show that in RBM, the major site of reactive oxygen species generation with glutamate or succinate is Co-I. We also found that Co-II generates substantial amounts of reactive oxygen species that increased 2-fold in the Rot-RBM. Our data suggest that the primary mechanism of the Rot toxic effect on RBM consists in a significant increase of O*2- generation that causes damage to Co-I and Co-II, presumably at the level of 4Fe-4S clusters. Decreased respiratory activity diminishes resistance of RBM to Ca2+ and thus increases probability of mPT and apoptotic cell death. We suggest that the damage to Co-I and Co-II shifts O*2- generation from the CoQ10 sites to more proximal sites, such as flavines, and makes it independent of the RBM functional state. 相似文献
824.
Tkachev AV Dobrotvorsky AK Vjalkov AI Morozov SV 《Experimental & applied acarology》2000,24(2):145-158
Chemical compositions of ethereal extracts of the body surface of unfed male and female Ixodes persulcatus ticks (Acari: Ixodidae) were studied by gas chromatography using mass-spectrometric detection. More than 100 different organic compounds were detected. The predominant components were saturated fatty hydrocarbons, saturated and unsaturated fatty acids, aldehydes, squalene, cholesterol and cholesterol derivatives. A number of compounds found in I. persulcatus are known as components of pheromones or constituents of dermal gland secretions in tick species of the genus Amblyomma: nonanoic acid, saturated fatty acids having from 14 to 16 carbons, and squalene. Saturated fatty aldehydes have not been reported previously as body surface components of hard ticks. Substituted phenols were not found in the extracts, although they are known as common components of sex and attraction–aggregation–attachment pheromones in Amblyomma ticks. With a few exceptions (henicosanal, 2,4-holestadiene and two unidentified cholesterol derivatives), there was no marked difference in composition of surface components between male and female I. persulcatus. The possible role of the different chemical groups in communication between I. persulcatus ticks is discussed. 相似文献
825.
Odintsov SG Sabała I Bourenkov G Rybin V Bochtler M 《Journal of molecular biology》2005,354(2):403-412
Aminopeptidase T (AmpT) from Thermus thermophilus is a metalloexopeptidase with no similarity to prototypical metallopeptidases with an HExxH or HxxEH motif. The crystal structure of the Staphylococcus aureus homologue of AmpT, which is known as aminopeptidase S (AmpS), has been reported recently. This structure revealed a dimeric protein with a very unusual, elongated shape and a large internal cavity. The active sites were found on the inner walls of the cavity and were entirely shielded from the environment, which suggested either that the dimer in the crystals was not physiologically relevant, or that an inactive conformation had been crystallized. Here, we show by gel-filtration and analytical ultracentrifugation that AmpT, like AmpS, forms dimers in solution, and we present the structure of AmpT in a crystal form with five protomers in the asymmetric unit. The five protomers take conformations that range from fully closed, as in the AmpS structure, to nearly open, so that the active site is almost directly accessible. The different conformations indicate flexibility between the AmpT N and C-domains, and explain how AmpT can be active, although the unusual AmpS dimerization mode applies to AmpT as well. 相似文献
826.
The size of the protein database (PDB) makes it now feasible to arrive at statistical conclusions regarding structural effects of crystal packing. These effects are relevant for setting upper practical limits of accuracy on protein modeling. Proteins whose crystals have more than one molecule in the asymmetric unit or whose structures were determined at least twice by X-ray crystallography were paired and their differences analyzed. We demonstrate a clear influence of crystal environment on protein structure, including backbone conformations, hinge-like motions and side-chain conformations. The positions of surface water molecules tend to be variable in different crystal environments while those of ligands are not. Structures determined by independent groups vary more than structures determined by the same authors. The use of different refinement methods is a major source for this effect. Our pair-wise analysis derives a practical limit to the accuracy of protein modeling. For different crystal forms, the limit of accuracy (C(alpha), root-mean-square deviation (RMSD)) is approximately 0.8A for the entire protein, which includes approximately 0.3A due to crystal packing. For organized secondary elements, the upper limit of C(alpha) RMSD is 0.5-0.6A while for loops or protein surface it reaches 1.0A. Twenty percent of exposed side- chains exhibit different chi(1+2) conformations with approximately half of the effect also resulting from crystal packing. A web based tool for analysis and graphic presentation of surface areas of crystal contacts is available (http://ligin.weizmann.ac.il/cryco). 相似文献
827.
Bobrovnik S 《Journal of biochemical and biophysical methods》2005,65(1):30-44
A new method for determining the binding parameters of ligand-receptor interaction is suggested. The method is based on the application of the so-called coordinate of dilution, suggested by us earlier. We demonstrated that it is possible to determine the binding characteristics of ligand-receptor interaction using either the measurement of the concentration of the ligand-receptor complex at a state of equilibrium or the concentration of free receptors at different dilutions of the studying ligand-receptor mixture. The method also allows the determination of the concentration of the ligand in a pre-existing ligand-receptor mixture without preliminary separation of the interacting counterparts. For this reason the suggested method could be especially useful when the studying very labile receptors for which purification from the corresponding ligand is very difficult or impossible. 相似文献
828.
Sergiev PV Lesnyak DV Kiparisov SV Burakovsky DE Leonov AA Bogdanov AA Brimacombe R Dontsova OA 《Nucleic acids research》2005,33(18):6048-6056
Ribosomes synthesize proteins according to the information encoded in mRNA. During this process, both the incoming amino acid and the nascent peptide are bound to tRNA molecules. Three binding sites for tRNA in the ribosome are known: the A-site for aminoacyl-tRNA, the P-site for peptidyl-tRNA and the E-site for the deacylated tRNA leaving the ribosome. Here, we present a study of Escherichia coli ribosomes with the E-site binding destabilized by mutation C2394G of the 23S rRNA. Expression of the mutant 23S rRNA in vivo caused increased frameshifting and stop codon readthrough. The progression of these ribosomes through the ribosomal elongation cycle in vitro reveals ejection of deacylated tRNA during the translocation step or shortly after. E-site compromised ribosomes can undergo translocation, although in some cases it is less efficient and results in a frameshift. The mutation affects formation of the P/E hybrid site and leads to a loss of stimulation of the multiple turnover GTPase activity of EF-G by deacylated tRNA bound to the ribosome. 相似文献
829.
Fluorescent proteins as a toolkit for in vivo imaging 总被引:10,自引:0,他引:10
Green fluorescent protein (GFP) from the jellyfish Aequorea victoria, and its mutant variants, are the only fully genetically encoded fluorescent probes available and they have proved to be excellent tools for labeling living specimens. Since 1999, numerous GFP homologues have been discovered in Anthozoa, Hydrozoa and Copepoda species, demonstrating the broad evolutionary and spectral diversity of this protein family. Mutagenic studies gave rise to diversified and optimized variants of fluorescent proteins, which have never been encountered in nature. This article gives an overview of the GFP-like proteins developed to date and their most common applications to study living specimens using fluorescence microscopy. 相似文献
830.
Yevdokimov YM Skuridin SG Nechipurenko YD Zakharov MA Salyanov VI Kurnosov AA Kuznetsov VD Nikiforov VN 《International journal of biological macromolecules》2005,36(1-2):103-115
We describe the formation and properties of nanoconstruction that consists of the double-stranded DNA molecules located at distance of 35-50 A in the spatial structure of particles of their cholesteric liquid-crystalline dispersions and cross-linked by artificial nanobridges. The resulting nanostructures possess the peculiar spatial and optical properties. 相似文献