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81.
Tomasz Borowski Valentin Georgiev Per E. M. Siegbahn 《Journal of molecular modeling》2010,16(11):1673-1677
Catalytic cycle intermediates of a representative extradiol dioxygenase, homoprotocatechuate 2,3-dioxygenase (HPCD), have
recently been characterized in crystallo by Kovaleva and Lipscomb. The structures of the identified species indicate that
the process of inserting oxygen into the catechol ring occurs stepwise, and involves an Fe(II)-alkylperoxo intermediate and
its O–O cleavage product: a gem diol species. In general, these findings corroborate the results of our previous computational
studies; however, the fact that the gem diol species is stable enough to be observed in the crystal form seems to be at odds
with the computational mechanistic data, which suggest that this intermediate should very readily and spontaneously convert
to the epoxide species. The key question then becomes what is actually observed in the X-ray experiments. Here we report additional
computational studies undertaken with the hope of clarifying this issue. The results obtained for active site models hosting
both the native and the alternative (4-sulfonylcatechol) substrate indicate that the stability of the gem diol species is
substantially increased if an electron and a proton are added. If this occurs somehow, the lifetime of the intermediate should
be sufficient to observe it. 相似文献
82.
Mikhail P. Moshkin Eugene A. Novikov Sergey E. Tkachev Valentin V. Vlasov 《BioEssays : news and reviews in molecular, cellular and developmental biology》2009,31(6):620-628
The morbidity of tick‐borne encephalitis (TBE) varies yearly by as much as 10‐fold among the people of Western Siberia. This long‐term variation is dependent on many factors such as the density of the tick populations, the prevalence of TBE virus (TBEV) among sub‐adult ticks, the yearly virulence of the TBEV, and prophylactic measures. Here we highlight the role of small mammal hosts in the circulation of TBEV through the ecosystem. Refining classical models of non‐viremic horizontal transmission, we emphasize the recently understood fact that the physiological and immunological status of the small mammal hosts affects the tick and virus‐host interactions. In addition to its theoretical interest, our approach may lead to some practical improvements in the precision of epidemiological forecasts and perhaps in forestalling the severity of outbreaks of TBE, or, at least, in forewarning medical authorities and the general public of impending TBE outbreaks. 相似文献
83.
Portet B Fabre N Roumy V Gornitzka H Bourdy G Chevalley S Sauvain M Valentin A Moulis C 《Phytochemistry》2007,68(9):1312-1320
The bioassay-guided purification of an n-hexane extract from the leaves of Piper hostmannianum var. berbicense led to the isolation of four monoterpene or prenyl-substituted dihydrochalcones (1a, 1b, 2, 3) as well as the known compounds 2',6'-dihydroxy-4'-methoxydihydrochalcone (4), linderatone (5), strobopinin (6), adunctin E (7) and (-)-methyllinderatin (8). Their structures were established on the basis of NMR and X-ray analysis. (-)-Methyllinderatin, linderatone and 2',6'-dihydroxy-4'-methoxydihydrochalcone exhibited the most potent antiplasmodial activity with IC50 values of 5.64, 10.33 and 12.69 microM, respectively against both chloroquine-sensitive and resistant strains of Plasmodium falciparum (F32,FcB1). The activity of (-)-methyllinderatin was confirmed in vivo against Plasmodium vinckei petteri in mice (80% of reduction of parasitemia) at a dose of 20 mg/kg/day. 相似文献
84.
The overproduction of TNF and other cytokines is associated with the pathophysiology of numerous diseases. Controlling cytokine synthesis and release is critical for preventing unrestrained inflammation and maintaining health. Recent studies identified an efferent vagus nerve-based mechanism termed "the cholinergic anti-inflammatory pathway" that controls cytokine production and inflammation. Here we review current advances related to the role of this pathway in neuro-immune interactions that prevent excessive inflammation. Experimental evidence indicates that vagus nerve cholinergic anti-inflammatory signaling requires alpha7 nicotinic acetylcholine receptors expressed on non-neuronal cytokine-producing cells. Alpha7 nicotinic acetylcholine receptor agonists inhibit cytokine release and protect animals in a variety of experimental lethal inflammatory models. Knowledge related to the cholinergic anti-inflammatory pathway can be exploited in therapeutic approaches directed towards counteracting abnormal chronic and hyper-activated inflammatory responses. 相似文献
85.
Edupuganti OP Antoci V King SB Jose B Adams CS Parvizi J Shapiro IM Zeiger AR Hickok NJ Wickstrom E 《Bioorganic & medicinal chemistry letters》2007,17(10):2692-2696
Self-protecting Ti6Al4V alloy pins were prepared by covalent bonding of bis(ethylene glycol) linkers, then vancomycin to the oxidized, aminopropylated Ti6Al4V alloy surface. Fluorescence modification-enabled estimation of yields of free amines on the metallic surface monolayer at each reaction step. The vancomycin-protected Ti6Al4V pins were not colonized by Staphylococcus aureus, even after 44days storage in physiological buffer. These results provide a basis for testing self-protection against S. aureus colonization in animal models. 相似文献
86.
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
87.
UmuD and RecA directly modulate the mutagenic potential of the Y family DNA polymerase DinB 总被引:3,自引:0,他引:3
DinB is the only translesion Y family DNA polymerase conserved among bacteria, archaea, and eukaryotes. DinB and its orthologs possess a specialized lesion bypass function but also display potentially deleterious -1 frameshift mutagenic phenotypes when overproduced. We show that the DNA damage-inducible proteins UmuD(2) and RecA act in concert to modulate this mutagenic activity. Structural modeling suggests that the relatively open active site of DinB is enclosed by interaction with these proteins, thereby preventing the template bulging responsible for -1 frameshift mutagenesis. Intriguingly, residues that define the UmuD(2)-interacting surface on DinB statistically covary throughout evolution, suggesting a driving force for the maintenance of a regulatory protein-protein interaction at this site. Together, these observations indicate that proteins like RecA and UmuD(2) may be responsible for managing the mutagenic potential of DinB orthologs throughout evolution. 相似文献
88.
Garavito G Bertani S Rincon J Maurel S Monje MC Landau I Valentin A Deharo E 《Parasite (Paris, France)》2007,14(2):135-140
Methylene blue (MB) is the oldest synthetic antimalarial. It is not used anymore as antimalarial but should be reconsidered. For this purpose we have measured its impact on both chloroquine sensitive and resistant Plasmodium strains. We showed that around 5 nM of MB were able to inhibit 50% of the parasite growth in vitro and that late rings and early trophozoites were the most sensitive stages; while early rings, late trophozoites and schizonts were less sensitive. Drug interaction study following fractional inhibitory concentrations (FIC) method showed antagonism with amodiaquine, atovaquone, doxycycline, pyrimethamine; additivity with artemether, chloroquine, mefloquine, primaquine and synergy with quinine. These results confirmed the interest of MB that could be integrated in a new low cost antimalarial combination therapy. 相似文献
89.
Enhanced suicidal death of erythrocytes from gene-targeted mice lacking the Cl-/HCO(3)(-) exchanger AE1 总被引:2,自引:0,他引:2
Akel A Wagner CA Kovacikova J Kasinathan RS Kiedaisch V Koka S Alper SL Bernhardt I Wieder T Huber SM Lang F 《American journal of physiology. Cell physiology》2007,292(5):C1759-C1767
Genetic defects of anion exchanger 1 (AE1) may lead to spherocytic erythrocyte morphology, severe hemolytic anemia, and/or cation leak. In normal erythrocytes, osmotic shock, Cl removal, and energy depletion activate Ca2+-permeable cation channels with Ca2+-induced suicidal erythrocyte death, i.e., surface exposure of phosphatidylserine, cell shrinkage, and membrane blebbing, all features typical for apoptosis of nucleated cells. The present experiments explored whether AE1 deficiency favors suicidal erythrocyte death. Peripheral blood erythrocyte numbers were significantly smaller in gene-targeted mice lacking AE1 (AE1/ mice) than in their wild-type littermates (AE1+/+ mice) despite increased percentages of reticulocytes (AE1/: 49%, AE1+/+: 2%), an indicator of enhanced erythropoiesis. Annexin binding, reflecting phosphatidylserine exposure, was significantly larger in AE1/erythrocytes/reticulocytes (10%) than in AE1+/+ erythrocytes (1%). Osmotic shock (addition of 400 mM sucrose), Cl removal (replacement with gluconate), or energy depletion (removal of glucose) led to significantly stronger annexin binding in AE1/ erythrocytes/reticulocytes than in AE1+/+ erythrocytes. The increase of annexin binding following exposure to the Ca2+ ionophore ionomycin (1 µM) was, however, similar in AE1/ and in AE1+/+ erythrocytes. Fluo3 fluorescence revealed markedly increased cytosolic Ca2+ permeability in AE1/ erythrocytes/reticulocytes. Clearance of carboxyfluorescein diacetate succinimidyl ester-labeled erythrocytes/reticulocytes from circulating blood was more rapid in AE1/ mice than in AE1+/+ mice and was accelerated by ionomycin treatment in both genotypes. In conclusion, lack of AE1 is associated with enhanced Ca2+ entry and subsequent scrambling of cell membrane phospholipids. annexin; cell volume; osmolarity; phosphatidylserine; energy depletion 相似文献
90.