排序方式: 共有18条查询结果,搜索用时 15 毫秒
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I. W. Althaus J. J. Chou A. J. Gonzales R. J. LeMay M. R. Deibel K. -C. Chou F. J. Kezdy D. L. Romero R. C. Thomas P. A. Aristoff W. G. Tarpley F. Reusser 《Cellular and molecular life sciences : CMLS》1994,50(1):23-28
The tetramer of ethylenesulfonic acid (U-9843) is a potent inhibitor of HIV-1 RT* and possesses excellent antiviral activity at nontoxic doses in HIV-1 infected lymphocytes grown in tissue culture. Kinetic studies of the HIV-1 RT-catalyzed RNA-directed DNA polymerase activity were carried out in order to determine if the inhibitor interacts with the template: primer or the deoxyribonucleotide triphosphate (dNTP) binding sites of the polymerase. Michaelis-Menten kinetics, which are based on the establishment of a rapid equilibrium between the enzyme and its substrates, proved inadequate for the analysis of the experimental data. The data were thus analyzed using steady-state Briggs-Haldane kinetics assuming that the template:primer binds to the enzyme first, followed by the binding of the dNTP and that the polymerase is a processive enzyme. Based on these assumptions, a velocity equation was derived which allows the calculation of all the specific forward and backward rate constants for the reactions occurring between the enzyme, its substrates and the inhibitor. The calculated rate constants are in agreement with this model and the results indicated that U-9843 acts as a noncompetitive inhibitor with respect to both the template:primer and dNTP binding sites. Hence, U-9843 exhibits the same binding affinity for the free enzyme as for the enzyme-substrate complexes and must inhibit the RT polymerase by interacting with a site distinct from the substrate binding sites. Thus, U-9843 appears to impair an event occurring after the formation of the enzyme-substrate complexes, which involves either an event leading up to the formation of the phosphoester bond, the formation of the ester bond itself or translocation of the enzyme relative to its template:primer following the formation of the ester bond. 相似文献
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Gribouval O Gonzales M Neuhaus T Aziza J Bieth E Laurent N Bouton JM Feuillet F Makni S Ben Amar H Laube G Delezoide AL Bouvier R Dijoud F Ollagnon-Roman E Roume J Joubert M Antignac C Gubler MC 《Nature genetics》2005,37(9):964-968
Autosomal recessive renal tubular dysgenesis is a severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (Potter phenotype). Absence or paucity of differentiated proximal tubules is the histopathological hallmark of the disease and may be associated with skull ossification defects. We studied 11 individuals with renal tubular dysgenesis, belonging to nine families, and found that they had homozygous or compound heterozygous mutations in the genes encoding renin, angiotensinogen, angiotensin converting enzyme or angiotensin II receptor type 1. We propose that renal lesions and early anuria result from chronic low perfusion pressure of the fetal kidney, a consequence of renin-angiotensin system inactivity. This is the first identification to our knowledge of a renal mendelian disorder linked to genetic defects in the renin-angiotensin system, highlighting the crucial role of the renin-angiotensin system in human kidney development. 相似文献
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Deltcheva E Chylinski K Sharma CM Gonzales K Chao Y Pirzada ZA Eckert MR Vogel J Charpentier E 《Nature》2011,471(7340):602-607
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R. Velasco Alonso J. Prieto Valtuena M. A. del Pozzo Perez M. I. Gonzales Guilabert L. Corporales Lopez 《Cellular and molecular life sciences : CMLS》1973,29(7):870-871
Resumen Se ha estudiado la relación existente entre la concentración de Ig. sericas y las poblaciones linfocitarias T y B en un grupo de sujetos ancianos, encontrandose un notable descenso de la transformación blasticá al tiempo que se incrementa el porcentage de linfocitos portadores de Ig. en su membrana. De nuestros resultados parece deducirse una relación entre el nivel de Ig. sericas y la población medulo-derivada. 相似文献
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Schmutz J Wheeler J Grimwood J Dickson M Yang J Caoile C Bajorek E Black S Chan YM Denys M Escobar J Flowers D Fotopulos D Garcia C Gomez M Gonzales E Haydu L Lopez F Ramirez L Retterer J Rodriguez A Rogers S Salazar A Tsai M Myers RM 《Nature》2004,429(6990):365-368
As the final sequencing of the human genome has now been completed, we present the results of the largest examination of the quality of the finished DNA sequence. The completed study covers the major contributing sequencing centres and is based on a rigorous combination of laboratory experiments and computational analysis. 相似文献