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101.
Ju P Pages G Riek RP Chen PC Torres AM Bansal PS Kuyucak S Kuchel PW Vandenberg JI 《The Journal of biological chemistry》2009,284(2):1000-1008
Ion flow in many voltage-gated K(+) channels (VGK), including the (human ether-a-go-go-related gene) hERG channel, is regulated by reversible collapse of the selectivity filter. hERG channels, however, exhibit low sequence homology to other VGKs, particularly in the outer pore helix (S5) domain, and we hypothesize that this contributes to the unique activation and inactivation kinetics in hERG K(+) channels that are so important for cardiac electrical activity. The S5 domain in hERG identified by NMR spectroscopy closely corresponded to the segment predicted by bioinformatics analysis of 676 members of the VGK superfamily. Mutations to approximately every third residue, from Phe(551) to Trp(563), affected steady state activation, whereas mutations to approximately every third residue on an adjacent face and spanning the entire S5 segment perturbed inactivation, suggesting that the whole span of S5 experiences a rearrangement associated with inactivation. We refined a homology model of the hERG pore domain using constraints from the mutagenesis data with residues affecting inactivation pointing in toward S6. In this model the three residues with maximum impact on activation (W563A, F559A, and F551A) face out toward the voltage sensor. In addition, the residues that when mutated to alanine, or from alanine to valine, that did not express (Ala(561), His(562), Ala(565), Trp(568), and Ile(571)), all point toward the pore helix and contribute to close hydrophobic packing in this region of the channel. 相似文献
102.
Hong Zhao Joy Innes David C Brooks Scott Reierstad Mehmet B Yilmaz Zhihong Lin Serdar E Bulun 《Reproductive biology and endocrinology : RB&E》2009,7(1):37
Background
Aromatase, the key enzyme in estrogen biosynthesis, is encoded by the Cyp19a1 gene. Thus far, 3 unique untranslated first exons associated with distinct promoters in the mouse Cyp19a1 gene have been described (brain, ovary, and testis-specific). It remains unknown whether aromatase is expressed in other mouse tissues via novel and tissue-specific promoters. 相似文献103.
Male and female of Odaginiceps korykosensis sp. n. (Copepoda, Harpacticoida, Tetragonicipitidae), collected in the intertidal zone of Kızkalesi beach along the Mediterranean coast of Turkey (Mersin Province), are described. The new species is the fifth member of the genus and can easily be distinguished from the other species by the presence of four setae/spines on the second endopodal segment of P4 and by the structure of the caudal rami. Previously, representatives of the genus Odaginiceps have been reported from Gulf of Mexico, off Bermuda and Kenya. Odaginiceps korykosensis sp. n. is the first record of the genus in the Mediterranean Sea. 相似文献
104.
Background
Eukaryotic cells strictly regulate the structure and assembly of their actin filament networks in response to various stimuli. The actin binding proteins that control filament assembly are therefore attractive targets for those who wish to reorganize actin filaments and reengineer the cytoskeleton. Unfortunately, the naturally occurring actin binding proteins include only a limited set of pointed-end cappers, or proteins that will block polymerization from the slow-growing end of actin filaments. Of the few that are known, most are part of large multimeric complexes that are challenging to manipulate.Methodology/Principal Findings
We describe here the use of phage display mutagenesis to generate of a new class of binding protein that can be targeted to the pointed-end of actin. These proteins, called synthetic antigen binders (sABs), are based on an antibody-like scaffold where sequence diversity is introduced into the binding loops using a novel “reduced genetic code” phage display library. We describe effective strategies to select and screen for sABs that ensure the generated sABs bind to the pointed-end surface of actin exclusively.Conclusions/Significance
From our set of pointed-end binders, we identify three sABs with particularly useful properties to systematically probe actin dynamics: one protein that caps the pointed end, a second that crosslinks actin filaments, and a third that severs actin filaments and promotes disassembly. 相似文献105.
Serdar Burmaoglu Oztekin Algul Arzu Gobek Derya Aktas Anil Mahmut Ulger Busra Gul Erturk 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):490-495
Owing to ever-increasing bacterial and fungal drug resistance, we attempted to develop novel antitubercular and antimicrobial agents. For this purpose, we developed some new fluorine-substituted chalcone analogs (3, 4, 9–15, and 20–23) using a structure–activity relationship approach. Target compounds were evaluated for their antitubercular efficacy against Mycobacterium tuberculosis H37Rv and antimicrobial activity against five common pathogenic bacterial and three common fungal strains. Three derivatives (3, 9, and 10) displayed significant antitubercular activity with IC50 values of ≤16,760. Compounds derived from trimethoxy substituent scaffolds with monofluoro substitution on the B ring of the chalcone structure exhibited superior inhibition activity compared to corresponding hydroxy analogs. In terms of antimicrobial activity, most compounds (3, 9, 12–14, and 23) exhibited moderate to potent activity against the bacteria, and the antifungal activities of compounds 3, 13, 15, 20, and 22 were comparable to those of reference drugs ampicillin and fluconazole. 相似文献
106.
107.
Glutamate/Aspartate transporters cotransport three Na+ and one H+ ions with the substrate and countertransport one K+ ion. The binding sites for the substrate and two Na+ ions have been observed in the crystal structure of the archeal homolog GltPh, while the binding site for the third Na+ ion has been proposed from computational studies and confirmed by experiments. Here we perform detailed free energy simulations of GltPh, giving a comprehensive characterization of the substrate and ion binding sites, and calculating their binding free energies in various configurations. Our results show unequivocally that the substrate binds after the binding of two Na+ ions. They also shed light into Asp/Glu selectivity of GltPh, which is not observed in eukaryotic glutamate transporters. 相似文献
108.
Conventionally stained, C- and Ag-NOR banded karyotypes of Guenther's vole, Microtus guentheri were studied from Turkey. The species possesses a karyotype of 2n = 54, NFa = 52 and NF = 54 in specimens from Kahramanmara? and Gaziantep provinces, whereas NF = 56 in females and NF = 55 in males were found in individuals from Kirikkale and Nev?ehir provinces. The X chromosome was a large acrocentric (NF = 54) or submetacentric (NF = 55, 56) while the Y chromosome was a small telocentric in all specimens examined. Blocks of constitutive heterochromatin were located in the pericentromeric areas of autosomes including the X chromosome. Nucleolar organizer regions (NORs) were located at the telomeric regions of the short arms of five acrocentric pairs and centromeric regions of two telocentric pairs in the Nev?ehir and Kirikkale specimens. 相似文献
109.
Tascilar ME Ozgen IT Abaci A Serdar M Aykut O 《Biological trace element research》2011,143(1):188-195
The quality of the diet of obese children is poor. Eating habits may alter micronutrient status in obese patients. In this
study, we determined the serum levels of selenium, zinc, vanadium, molybdenum, iron, copper, beryllium, boron, chromium, manganese,
cobalt, silver, barium, aluminum, nickel, cadmium, mercury, and lead in obese Turkish children. Thirty-four obese and 33 healthy
control subjects were enrolled in the study. Serum vanadium and cobalt levels of obese children were significantly lower than
those of the control group (0.244 ± 0.0179 vs. 0.261 ± 0.012 μg/l, p < 0.001, and 0.14 ± 0.13 vs. 0.24 ± 0.15 μg/l, p = 0.011, respectively). There was no significant difference between groups regarding the other serum trace element levels.
In conclusion, there may be alterations in the serum levels of trace elements in obese children and these alterations may
have a role in the pathogenesis of obesity. 相似文献
110.