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61.
Active state of sensory rhodopsin II: structural determinants for signal transfer and proton pumping
Gushchin I Reshetnyak A Borshchevskiy V Ishchenko A Round E Grudinin S Engelhard M Büldt G Gordeliy V 《Journal of molecular biology》2011,412(4):591-600
The molecular mechanism of transmembrane signal transduction is still a pertinent question in cellular biology. Generally, a receptor can transfer an external signal via its cytoplasmic surface, as found for G-protein-coupled receptors such as rhodopsin, or via the membrane domain, such as that in sensory rhodopsin II (SRII) in complex with its transducer, HtrII. In the absence of HtrII, SRII functions as a proton pump. Here, we report on the crystal structure of the active state of uncomplexed SRII from Natronomonas pharaonis, NpSRII. The problem with a dramatic loss of diffraction quality upon loading of the active state was overcome by growing better crystals and by reducing the occupancy of the state. The conformational changes in the region comprising helices F and G are similar to those observed for the NpSRII-transducer complex but are much more pronounced. The meaning of these differences for the understanding of proton pumping and signal transduction by NpSRII is discussed. 相似文献
62.
A cosmid gene bank of partially EcoRI-digested genomic DNA from Methylobacterium extorquens IBT no. 6 was screened for DNA fragments restoring polyhydroxyalkanoic-acid (PHA) accumulation in the PHA-negative mutant Alkaligenes eutrophus H16 PHB–4. The M. extorquens PHA-synthase structural gene phaC
Mex
was mapped on a 23-kbp EcoRI fragment by complementation studies, by hybridization experiments with heterologous DNA probes from A. eutrophus H16 encoding for phaA, phaB and phaC and by nucleic acid sequence analysis. Evidence for the presence of genes for a -ketothiolase or an acetoacetyl-coenzyme A reductase on this fragment was not obtained. The nucleotide sequence of a 3.7-kbp region was obtained. It contained the entire 1.815-kbp phaC
Mex plus approximately each 900-bp upstream and downstream of phaC
Mex. PhaC
Mex
encoded a protein of 605 amino acods with a relative molecular mass (Mr) of 66742, which exhibited 38.1% amino acid identity with the A. eutrophus PHA synthase. Determination of the N-terminal amino acid sequence of an Mr 65 000 protein, which was enriched concomitantly with the purification of PHA granules in sucrose gradients, revealed a sequence that was identical with the amino acid sequence deduced from the most probable translation start codon except for a valine, which was obviously removed post-translationally. Enzyme analysis, which was done with the native gene and a phaC
Mex
-lacZ fusion gene, gave no evidence for expression of phaC
Mex
in Escherichia coli. 相似文献
63.
Valentin Soulard 《Free radical research》2016,50(10):S2-S5
AbstractA thiophenol-mediated method for the conversion of propargylamines to pyrrolidines under acidic conditions is described. This cascade reaction involves addition of a thiyl radical to the terminal alkyne followed by a 1,5-hydrogen transfer (radical translocation) and a rapid cyclization affording the pyrrolidine ring. Our studies reveal that complete protonation of the tertiary amine with 10 equivalents of trifluoroacetic acid avoids undesired hydrogen atom abstractions by the thiyl radicals. 相似文献
64.
We analysed monthly samples collected in Guanabara Bay, with a conical net of 200 m mesh during 1985. The bay was divided into three areas: an outer region (area A), influenced by oceanic waters; an inner region (area C), influenced by fluvial inflow; and a transition region (area B) with intermediate features. Penilia avirostris and Evadne tergestina were observed in the three areas, with greatest densities, however, in the outermost region, which had the highest salinities and lowest temperatures. Penilia avirostris was more abundant in summer (March), a period with the greatest relative densities of nanoplankton. Evadne tergestina was also abundant in summer, but its peak fell in November, a period with a relative increase in microphytoplankton density in the bay. The two species disappeared in winter: Penilia avirostris was absent from May to August, whereas Evadne tergestina disappeared in August and September. 相似文献
65.
Suman Kundu Talat Roome Ashish Bhattacharjee Kevin A. Carnevale Valentin P. Yakubenko Renliang Zhang Sung Hee Hwang Bruce D. Hammock Martha K. Cathcart 《Journal of lipid research》2013,54(2):436-447
Monocyte chemoattractant protein-1 (MCP-1)-induced monocyte chemotaxis is a major event in inflammatory disease. Our prior studies have demonstrated that MCP-1-dependent chemotaxis requires release of arachidonic acid (AA) by activated cytosolic phospholipase A2 (cPLA2). Here we investigated the involvement of AA metabolites in chemotaxis. Neither cyclooxygenase nor lipoxygenase pathways were required, whereas pharmacologic inhibitors of both the cytochrome-P450 (CYP) and the soluble epoxide hydrolase (sEH) pathways blocked monocyte chemotaxis to MCP-1. To verify specificity, we demonstrated that the CYP and sEH products epoxyeiscosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs), respectively, restored chemotaxis in the presence of the inhibitors, indicating that sEH-derived products are essential for MCP-1-driven chemotaxis. Importantly, DHETs also rescued chemotaxis in cPLA2-deficient monocytes and monocytes with blocked Erk1/2 activity, because Erk controls cPLA2 activation. The in vitro findings regarding the involvement of CYP/sEH pathways were further validated in vivo using two complementary approaches measuring MCP-1-dependent chemotaxis in mice. These observations reveal the importance of sEH in MCP-1-regulated monocyte chemotaxis and may explain the observed therapeutic value of sEH inhibitors in treatment of inflammatory diseases, cardiovascular diseases, pain, and even carcinogenesis. Their effectiveness, often attributed to increasing EET levels, is probably influenced by the impairment of DHET formation and inhibition of chemotaxis. 相似文献
66.
67.
Pavel Bobrovsky Valentin Manuvera Izolda Baskova Svetlana Nemirova Alexandr Medvedev Vassili Lazarev 《Current issues in molecular biology》2021,43(3):2068
Leeches are amazing animals that can be classified as conditionally poisonous animals since the salivary cocktail they produce is injected directly into the victim, and its components have strictly defined biological purposes, such as preventing blood clot formation. Thrombolytic drugs are mainly aimed at treating newly formed blood clots. Aged clots are stabilized by a large number of isopeptide bonds that prevent the action of thrombolytics. These bonds are destroyed by destabilase, an enzyme of the leech’s salivary glands. Here, we conducted a pilot study to evaluate the feasibility and effectiveness of the use of destabilase in relation to blood clots formed during real pathological processes. We evaluated the isopeptidase activity of destabilase during the formation of a stabilized fibrin clot. We showed that destabilase does not affect the internal and external coagulation cascades. We calculated the dose–response curve and tested the ability of destabilase to destroy isopeptide bonds in natural blood clots. The effect of aged and fresh clots dissolving ability after treatment with destabilase coincided with the morphological characteristics of clots during surgery. Thus, recombinant destabilase can be considered as a potential drug for the treatment of aged clots, which are difficult to treat with known thrombolytics. 相似文献
68.
The vascular system is unique in that extensive branching morphogenesis may take place in the adult. Developmental neovascularization is guided by precise spatial cues but vessel formation in the adult is not genetically programmed. Here, we review different adult modes for branch patterning, acquiring artery or vein identity and allocating vascular progenitor cells. The endothelium shows a remarkable degree of self-organization into a treelike network and hemodynamic forces are important in rectifying abnormal branching. This discussion is in the context of a contemplated therapy for improving organ perfusion by creating new vascular loops properly integrated within the existing network. 相似文献
69.
Dragoi V 《Biological cybernetics》2002,86(6):419-426
Simple exposure to repeatitive stimulation is known to induce short-term learning effects across a wide range of species.
These effects can be both suppressive and facilitatory depending on stimulus conditions: repeatitive presentation of a weak
stimulus decreases the strength of the response (habituation), whereas presentation of a tonic stimulus following a series
of weak stimuli transiently increases the response strength (dishabituation). Although these phenomena have been comprehensively
characterized at both behavioral and cellular levels, most existing models of nonassociative learning focus exclusively on
the suppressive or facilitatory changes in response, and do not attempt to relate cellular events to behavior. I propose here
a feedforward model of habituation effects that explains both suppressive and facilitatory changes in response relying on
the interaction between excitatory and inhibitory processes that develop in parallel on two different timescales. The model's
properties are used to explain the rate sensitivity property of habituation and recovery and stimulus dishabituation.
Received: 1 June 2001 / Accepted in revised form: 4 December 2001 相似文献
70.
Dourlat J Valentin B Liu WQ Garbay C 《Bioorganic & medicinal chemistry letters》2007,17(14):3943-3946
Investigation within the pTyr-binding pocket of the STAT3 SH2 domain led us to develop a novel synthesis of two pTyr mimetics, l-tetrazolylmethylphenylalanine (l-Tmp) and l-O-malonyltyrosine (l-OMT), that were next incorporated in a high affinity ligand of STAT3 SH2 domain. Biological evaluation of peptidomimetics on STAT3 dimerization identified l-OMT as the first non-phosphorus pTyr mimetic so far reported against STAT3 SH2 domain, harboring an activity similar to that of the Pmp-containing reference peptidomimetic. 相似文献