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191.
Perez-Jimenez R Wiita AP Rodriguez-Larrea D Kosuri P Gavira JA Sanchez-Ruiz JM Fernandez JM 《The Journal of biological chemistry》2008,283(40):27121-27129
Understanding how the catalytic mechanisms of enzymes are optimized through evolution remains a major challenge in molecular biology. The concept of co-evolution implicates that compensatory mutations occur to preserve the structure and function of proteins. We have combined statistical analysis of protein sequences with the sensitivity of single molecule force-clamp spectroscopy to probe how catalysis is affected by structurally distant correlated mutations in Escherichia coli thioredoxin. Our findings show that evolutionary anti-correlated mutations have an inhibitory effect on enzyme catalysis, whereas positively correlated mutations rescue the catalytic activity. We interpret these results in terms of an evolutionary tuning of both the enzyme-substrate binding process and the chemistry of the active site. Our results constitute a direct observation of distant residue co-evolution in enzyme catalysis. 相似文献
192.
Marsillach J Ferré N Camps J Rull A Beltran R Joven J 《Molecular and cellular biochemistry》2008,308(1-2):101-109
Chronic liver diseases are accompanied by changes in the biochemical pathways related to the regulation of apoptosis and extra-cellular
matrix deposition. The present study was designed to investigate, using low density arrays, changes in the hepatic gene expression
together with hepatic biochemical and histological alterations in rats that had liver impairment induced by chronic exposure
to CCl4. Further, we examined the possible recovery of genetic and pathological changes following the cessation of the hepatotoxic
injury. Experimental fibrosis was induced in male Wistar rats by CCl4 administration. Animals were subdivided into two groups. One group was given CCl4 and animals were killed at 8 and 12 weeks of treatment. The other group was treated with CCl4 for 6 weeks, the CCl4 was then stopped and, subsequently, subgroups of animals were killed after 1 and 2 weeks of recovery. CCl4 administration over 12 weeks was associated with significant changes in B-cell leukemia/lymphoma 2, procollagen type I α
2, matrix metalloproteinases 3 and 8, tissue inhibitors of metalloproteinases 1, 2, and 3 and the inhibitor of apoptosis 4
gene expressions. Recovery after CCl4 cessation was associated with changes in procollagen type I α 2, matrix metalloproteinase 7, tissue inhibitors of metalloproteinases
1 and 2, inhibitor of apoptosis 4, and survivin gene expressions. This study shows an association between changes in the expression
of several genes regulating hepatic cell apoptosis, the fibrosis process, and the recovery of the hepatic function after removal
of the toxic injury. 相似文献
193.
The dimeric cytochrome bc(1) complex catalyzes the oxidation-reduction of quinol and quinone at sites located in opposite sides of the membrane in which it resides. We review the kinetics of electron transfer and inhibitor binding that reveal functional interactions between the quinol oxidation site at center P and quinone reduction site at center N in opposite monomers in conjunction with electron equilibration between the cytochrome b subunits of the dimer. A model for the mechanism of the bc(1) complex has emerged from these studies in which binding of ligands that mimic semiquinone at center N regulates half-of-the-sites reactivity at center P and binding of ligands that mimic catalytically competent binding of ubiquinol at center P regulates half-of-the-sites reactivity at center N. An additional feature of this model is that inhibition of quinol oxidation at the quinone reduction site is avoided by allowing catalysis in only one monomer at a time, which maximizes the number of redox acceptor centers available in cytochrome b for electrons coming from quinol oxidation reactions at center P and minimizes the leakage of electrons that would result in the generation of damaging oxygen radicals. 相似文献
194.
Energy transduction in the cytochrome bc(1) complex is achieved by catalyzing opposite oxido-reduction reactions at two different quinone binding sites. We have determined the pre-steady state kinetics of cytochrome b and c(1) reduction at varying quinol/quinone ratios in the isolated yeast bc(1) complex to investigate the mechanisms that minimize inhibition of quinol oxidation at center P by reduction of the b(H) heme through center N. The faster rate of initial cytochrome b reduction as well as its lower sensitivity to quinone concentrations with respect to cytochrome c(1) reduction indicated that the b(H) hemes equilibrated with the quinone pool through center N before significant catalysis at center P occurred. The extent of this initial cytochrome b reduction corresponded to a level of b(H) heme reduction of 33%-55% depending on the quinol/quinone ratio. The extent of initial cytochrome c(1) reduction remained constant as long as the fast electron equilibration through center N reduced no more than 50% of the b(H) hemes. Using kinetic modeling, the resilience of center P catalysis to inhibition caused by partial pre-reduction of the b(H) hemes was explained using kinetics in terms of the dimeric structure of the bc(1) complex which allows electrons to equilibrate between monomers. 相似文献
195.
196.
Dharmesh S. Kapoor G. Willy Davila Raul J. Rosenthal Gamal M. Ghoniem 《Obesity (Silver Spring, Md.)》2004,12(7):1104-1107
Objective: The objective of this study was to evaluate the impact of obesity on pelvic floor function in women. Research Methods and Procedures: This was a prospective controlled study of 20 morbidly obese female patients planning to undergo gastric bypass surgery and 20 age‐matched female controls. Subjects completed symptom and impact questionnaires, including the Incontinence Impact Questionnaire (IIQ‐7), Urogenital Distress Inventory (UDI), the Kobashi Prolapse Symptom Inventory and Quality‐of‐Life Questionnaire (PSI‐QOL), and Index of Female Sexual Function. Data were analyzed with Wilcoxon or ratio χ2 tests. Results: Mean weight was 295.7 ± 87.9 lbs in the study group and 144.79 ± 33.07 lbs in the control group. Mean BMI was 52.65 ±14.49 kg/m2 in the study group and 25.11 ± 5.27 kg/m2 in the control group. According to the IIQ‐7, urinary incontinence significantly affected lifestyle in the study group. The total IIQ‐7 score was also significantly affected in the study group (p = 0.03). The UDI indicated more urinary leakage with activity (p = 0.04) and more incidents of small amounts of leakage (p = 0.02) in the study group. According to the PSI‐QOL, women in the study group experienced constipation more often because of difficulty in emptying the rectum (p = 0.04). The PSI‐QOL score was higher in the study group (6.75 ± 6.84) than in the control group (2.65 ± 3.03; p = 0.04). There were no significant differences between groups regarding sexual function. Discussion: Morbid obesity is associated with a significant negative impact on urogenital health. Sexual function did not seem to be affected in women who are morbidly obese. 相似文献
197.
Energy transduction in the cytochrome bc1 complex is achieved by catalyzing opposite oxido-reduction reactions at two different quinone binding sites. We have determined the pre-steady state kinetics of cytochrome b and c1 reduction at varying quinol/quinone ratios in the isolated yeast bc1 complex to investigate the mechanisms that minimize inhibition of quinol oxidation at center P by reduction of the bH heme through center N. The faster rate of initial cytochrome b reduction as well as its lower sensitivity to quinone concentrations with respect to cytochrome c1 reduction indicated that the bH hemes equilibrated with the quinone pool through center N before significant catalysis at center P occurred. The extent of this initial cytochrome b reduction corresponded to a level of bH heme reduction of 33%–55% depending on the quinol/quinone ratio. The extent of initial cytochrome c1 reduction remained constant as long as the fast electron equilibration through center N reduced no more than 50% of the bH hemes. Using kinetic modeling, the resilience of center P catalysis to inhibition caused by partial pre-reduction of the bH hemes was explained using kinetics in terms of the dimeric structure of the bc1 complex which allows electrons to equilibrate between monomers. 相似文献
198.
199.
Raul Narciso C. Guedes Robert H. Smith† Nelsa Maria P. Guedes† 《Physiological Entomology》2003,28(4):298-305
Abstract. Variation between strains of Callosobruchus maculatus in several life-history traits is well known. Differences in functional anatomy of egg pores and larval respiration rates have also been reported in strains from Brazil and Yemen. The response of five strains of C. maculatus to seeds of two host species, cowpea ( Vigna unguiculata ) and mung bean ( Vigna radiata ), was measured along with the larval respiration rates of the same strains on both hosts. There was significant variability of response to the two hosts. Strains with higher larval respiration rate (µL O2 /insect/day) showed higher seed consumption, which significantly affected adult emergence per seed on both hosts. This finding provides support for the hypothesis that differential feeding rate is an important mechanistic component of the larval competition outcome observed in strains of C. maculatus . 相似文献
200.
Walter Goldschmidt 《Human Evolution》2003,18(1-2):97-112