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941.
Rusconi S Innocenti A Vullo D Mastrolorenzo A Scozzafava A Supuran CT 《Bioorganic & medicinal chemistry letters》2004,14(23):5763-5767
A detailed inhibition study of five carbonic anhydrase (CA, EC 4.2.1.1) isozymes with inorganic phosphates, carbamoyl phosphate, the antiviral phosphonate foscarnet as well as formate is reported. The cytosolic isozyme hCA I was weakly inhibited by neutral phosphate, strongly inhibited by carbamoyl phosphate (K(I) of 9.4 microM), and activated by hydrogen- and dihydrogenphosphate, foscarnet and formate (best activator foscarnet, K(A)=12 microM). The cytosolic isozyme hCA II was weakly inhibited by all the investigated anions, with carbamoyl phosphate showing a K(I) of 0.31 mM. The membrane-associated isozyme hCA IV was the most sensitive to inhibition by phosphates/phosphonates, showing a K(I) of 84 nM for PO(4)(3-), of 9.8 microM for HPO(4)(2-), and of 9.9 microM for carbamoyl phosphate. Foscarnet was the best inhibitor of this isozyme (K(I) of 0.82 mM) highly abundant in the kidneys, which may explain some of the renal side effects of the drug. The mitochondrial isozyme hCA V was weakly inhibited by all phosphates/phosphonates, except carbamoyl phosphate, which showed a K(I) of 8.5 microM. Thus, CA V cannot be the isozyme involved in the carbamoyl phosphate synthetase I biosynthetic reaction, as hypothesized earlier. Furthermore, the relative resistance of CA V to inhibition by inorganic phosphates suggests an evolutionary adaptation of this mitochondrial isozyme to the presence of high concentrations of such anions in these energy-converting organelles, where high amounts of ATP are produced by ATP synthetase, from ADP and inorganic phosphates. The transmembrane, tumor-associated isozyme hCA IX was on the other hand slightly inhibited by all these anions. 相似文献
942.
Walters I Bennion C Connolly S Croshaw PJ Hardy K Hartopp P Jackson CG King SJ Lawrence L Mete A Murray D Robinson DH Stein L Wells E John Withnall W 《Bioorganic & medicinal chemistry letters》2004,14(14):3645-3649
The high lipophilicity of a series of cytosolic phospholipase A(2) inhibitors has been reduced by the modification of a decyloxyphenyl chain designed to mimic the arachidonyl group of the natural substrate. These changes have resulted in an improvement in the whole cell potency of the inhibitors. 相似文献
943.
da Silva AJ Coelho AL Simas AB Moraes RA Pinheiro DA Fernandes FF Arruda EZ Costa PR Melo PA 《Bioorganic & medicinal chemistry letters》2004,14(2):431-435
Edunol (3), a pterocarpan isolated from Harpalyce brasiliana, a plant used in the northeast of Brazil against snakebites, was obtained by synthesis and showed antimyotoxic, antiproteolytic and PLA2 inhibitor properties. These proprieties could be improved through the synthesis of a bioisoster (5), where the prenyl group was replaced by the benzyl group. 相似文献
944.
Altes A Ruiz A Barceló MJ Remacha AF Puig T Maya AJ Castell C Amate JM Saz Z Baiget M 《Genetic testing》2004,8(4):407-410
In Spain, 85% of patients with genetic hemochromatosis (GH) are homozygous for the C282Y mutation of the HFE gene. H63D and S65C mutations of HFE may also play some role in the disease. The aim of this study was to establish the prevalence of C282Y, H63D, and S65C mutations of the HFE gene in newborns in Catalonia, Spain. One thousand one hundred forty-six newborn screening cards were selected randomly. DNA from these cards was extracted and HFE mutations were analyzed with the LightCycler equipment (Roche Diagnostics Gmbh, Mannheim, Germany). Sufficient DNA sample was obtained to screen for the three mutations in 1,043 cases (91%). The allelic frequencies of C282Y, H63D, and S65C mutations were 0.03 (IC 95% 0.022-0.037), 0.2 (IC 95% 0.19-0.22), and 0.01 (95% confidence interval [CI] 0.006-0.015), respectively. The frequency of C282Y homozygous newborns was 0.001 (95% CI 0.0005-0.0014). The frequencies of newborns doubly heterozygous for C282Y/H63D and C282Y/S65C were 0.01 (95% CI 0.005-0.02) and 0.002 (95% CI 0.0002-0.01), respectively. The allelic frequency of C282Y mutation is similar to that observed in Southern France, in the Czech Republic and in some areas of Italy. The allelic frequency of H63D mutation in Catalonia is the highest reported to date. Nevertheless, S65C is infrequent. These data should be kept in mind when designing hemochromatosis genotypic screening programs in Catalonia. 相似文献
945.
Cejas JR Almansa E Jérez S Bolaños A Felipe B Lorenzo A 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2004,139(2):209-216
To establish the changes which occur during embryogenesis and early larvae development, eggs, yolk-sac larvae (one day old larvae) and absorbed yolk-sac larvae (three day old larvae) of white sea bream were examined for lipid class and fatty acid composition. The development was characterized by a decrease in all lipid classes with the exception of phosphatidylserine (PS) and fatty free acids (FFA) which increased, and sphingomyelin (SM) which remained unchanged. The changes observed in lipid class content and the decrease in fatty acids in total lipid (TL) reflect the utilization and mobilization of lipids during both embryogenesis and early larvae development. Fluctuations in the relative composition of fatty acids in phosphatidylcholine (PC) during development suggest a selective bulk uptake and catabolism of fatty acids in this lipid class. Unlike PC, catabolism of triacylglycerol (TG) fatty acid appears to be non-selective. During development, the decrease in levels of polyunsaturated fatty acids (PUFA) eicosapentaenoic (20:5n-3, EPA) and docosahexaenoic (22:6n-3, DHA) in total lipid denotes their utilization as energy substrate by Diplodus sargus larvae. 相似文献
946.
Cejas JR Almansa E Jérez S Bolaños A Samper M Lorenzo A 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2004,138(1):91-102
Total lipids (TL), lipid classes, and their associated fatty acids from muscle and liver of captive and wild mature female broodstocks were investigated in order to estimate the fatty acid requirements of white seabream (Diplodus sargus). The results showed that the percentage of triacylglycerol was higher in liver and muscle of captive fish than in wild fish. The distribution of phospholipid classes in liver and muscle of both fish groups was similar, phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol being the predominant lipid classes. The general pattern of fatty acid distribution in total lipid of liver and muscle from captive and wild fish was similar. However, the relative percentage of specific fatty acids differed in captive and wild fish. The most noteworthy difference was the lower proportion of arachidonic acid (20:4n-6, AA) and the higher proportion of eicosapentaenoic acid (20:5n-3, EPA) in liver and muscle of captive fish with respect to those of wild fish. The proportion of docosahexaenoic acid (22:6n-3, DHA) did not differ between the two fish groups. The differences in EPA and AA proportions between captive and wild fish implied that captive fish presented a higher EPA/AA ratio and a lower DHA/EPA ratio than wild fish. In general terms, in both liver and muscle, the differences in fatty acid composition observed for TL were extended to all lipid classes. The results suggest that the different AA, EPA and DHA proportions in liver and muscle between captive and wild broodstocks are attributed to different levels of these fatty acids in broodstock diets. 相似文献
947.
Camargos ER Rocha LL Rachid MA Almeida AP Ferreira AJ Teixeira AL Chiari E Barton M Teixeira MM Machado CR 《Microbes and infection / Institut Pasteur》2004,6(7):650-656
Chagas' disease, caused by Trypanosoma cruzi, has an acute phase characterized by blood-circulating trypomastigotes and amastigote proliferation in several cell types, especially muscle cells. In the chronic phase, around 70% of infected people are asymptomatic (latent form). The remainder develop chagasic cardiomyopathy and/or digestive syndromes. There is evidence for aggravation of the chronic cardiac pathology by endothelin-mediated vasoconstriction. Holtzman rats have proven to be a good model for Chagas' disease acute phase and latent chronic phase. Now, we investigate the effects of prolonged treatment with an endothelin ET(A) receptor antagonist, BSF 461314, during the acute phase on parasitemia, coronary flow, tissue parasitism and the inflammatory process. Using isolated heart in Langendorff's preparation, endothelial dysfunction was observed only in non-treated infected animals. Histoquantitative analyses carried out in heart and diaphragm showed higher tissue parasitism and/or inflammatory process in BSF 461314-treated animals. Our data indicate that endothelin ET(A) receptors contribute to the initial mechanisms of parasite control. Impairment of the endothelium-dependent vasodilatation favors hazardous effects. However, blocking endothelin ET(A) receptors can prevent the latter. 相似文献
948.
Pérez AJ Perez-Iratxeta C Bork P Thode G Andrade MA 《Bioinformatics (Oxford, England)》2004,20(13):2084-2091
949.
A hint to search for metalloproteins in gene banks 总被引:1,自引:0,他引:1
MOTIVATION: With the advent of genome sequencing, a huge database of protein primary sequences has been accumulating. In parallel, a number of tools to investigate and expand upon this information, e.g. reconstructing and building relationships between protein families and superfamilies, have been developed. Metalloproteins are proteins capable of binding one or more metal ions, which are required for their biological function or for regulation of their activities or for structural purposes. Sometimes, metal binding can be observed in vitro but not be physiologically relevant. At present, there is a lack of specific tools to address the matter of the identification of metalloproteins in databases of gene sequences. RESULTS: In the present work, an approach exploiting metal-binding patterns (MBPs) of metalloproteins present in the Protein Data Bank to search gene banks for new metalloproteins is presented and applied to copper proteins. Nearly 100 different MBPs have been identified and then used for subsequent applications. The ensemble of sequences of the whole PDB is used to assess the potentiality and limits of the method and to identify levels of confidence for the predictions output by the search. It appears that copper-binding capabilities are identified with a confidence >90% when the percentage of identical amino acids aligned around the MBP by PHI-BLAST is at least 20% with respect to the entire protein domain length. If this percentage is between 10% and 20%, the level of confidence is approximately 50%. Application of the methodology to the entire genome sequences of Pyrococcus furiosus, Escherichia coli, Drosophila melanogaster and Homo sapiens suggests some differentiation between prokaryotes and eukaryotes. SUPPLEMENTARY INFORMATION: A table reporting statistics on the MBP identified; a list of all hits retrieved for the four organisms considered; a figure showing the number of hits for the four organisms as a function of I(d)(Global). 相似文献
950.
Domínguez Antonio Cervera Magdalena Pérez Rosa M. Romero Juan Fagoaga Carmen Cubero Jaime López María M. Juárez José A. Navarro Luis Peña Leandro 《Molecular breeding : new strategies in plant improvement》2004,14(2):171-183
Genetic transformation has been achieved for several citrus genotypes. However, regeneration of escapes at high frequency is a major problem, making the available procedures rather inefficient. Attempts to improve selection by increasing the concentration of kanamycin, used as the selective agent, or substituting it by geneticin have been unsuccessful. Here, we have critically assessed the actual frequency and origin of escapes in citrus by using visual screening with -glucuronidase (gusA) and green fluorescent protein (gfp) markers, by studying the persistence of engineered Agrobacterium in the explants, and by characterising through Southern blot analysis all the regenerants obtained under kanamycin selection. Our results show that inefficient selection could be attributed to the protection of the non-transformed cells from the selective agent by the surrounding transformed cells, and to the persistence of kanamycin-resistance Agrobacterium in explant tissues over long periods of time after co-cultivation. This also explained the high frequency (12%) of chimeric shoots that were commonly recovered. High frequency regeneration of chimeras that resulted from the fusion of different transformation events is reported for the first time. On the other hand, molecular analysis of all the regenerants reveals that transformation frequency is underestimated when based on the expression of a screenable marker gene, and that low expressors and silenced lines could account for at least 25% of those plants considered escapes based on selectable and screenable marker analysis. Consequences of these results at the practical level are also discussed. 相似文献