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991.
扩张型心肌病是一种以左心室和,或右心室扩大、心肌收缩功能受损为主要特征的心肌疾病,是除冠心病和高血压以外导致心力衰竭的主要病因之一。家族性扩张型心肌病约占扩张型心肌病的35%。目前为止,发现的和扩张型心肌病相关的基因突变主要是心肌蛋白基因突变和细胞骨架蛋白基因突变,此外还有线粒体DNA的突变和能量代谢相关的基因突变。本文对引起家族性扩张型心肌病的分子遗传进展进行了总结。 相似文献
992.
Vorobiev SM Neely H Seetharaman J Ma LC Xiao R Acton TB Montelione GT Tong L 《Protein science : a publication of the Protein Society》2007,16(3):535-538
We report here the crystal structure at 2.0 A resolution of the AGR_C_4470p protein from the Gram-negative bacterium Agrobacterium tumefaciens. The protein is a tightly associated dimer, each subunit of which bears strong structural homology with the two domains of the heme utilization protein ChuS from Escherichia coli and HemS from Yersinia enterocolitica. Remarkably, the organization of the AGR_C_4470p dimer is the same as that of the two domains in ChuS and HemS, providing structural evidence that these two proteins evolved by gene duplication. However, the binding site for heme, while conserved in HemS and ChuS, is not conserved in AGR_C_4470p, suggesting that it probably has a different function. This is supported by the presence of two homologs of AGR_C_4470p in E. coli, in addition to the ChuS protein. 相似文献
993.
Combining substrate dynamics, binding statistics, and energy barriers to rationalize regioselective hydroxylation of octane and lauric acid by CYP102A1 and mutants 下载免费PDF全文
Feenstra KA Starikov EB Urlacher VB Commandeur JN Vermeulen NP 《Protein science : a publication of the Protein Society》2007,16(3):420-431
Hydroxylations of octane and lauric acid by Cytochrome P450-BM3 (CYP102A1) wild-type and three active site mutants--F87A, L188Q/A74G, and F87V/L188Q/A74G--were rationalized using a combination of substrate orientation from docking, substrate binding statistics from molecular dynamics simulations, and barrier energies for hydrogen atom abstraction from quantum mechanical calculations. Wild-type BM3 typically hydroxylates medium- to long-chain fatty acids on subterminal (omega-1, omega-2, omega-3) but not the terminal (omega) positions. The known carboxylic anchoring site Y51/R47 for lauric acid, and hydrophobic interactions and steric exclusion, mainly by F87, for octane as well as lauric acid, play a role in the binding modes of the substrates. Electrostatic interactions between the protein and the substrate strongly modulate the substrate's regiodependent activation barriers. A combination of the binding statistics and the activation barriers of hydrogen-atom abstraction in the substrates is proposed to determine the product formation. Trends observed in experimental product formation for octane and lauric acid by wild-type BM3 and the three active site mutants were qualitatively explained. It is concluded that the combination of substrate binding statistics and hydrogen-atom abstraction barrier energies is a valuable tool to rationalize substrate binding and product formation and constitutes an important step toward prediction of product ratios. 相似文献
994.
Musayev FN di Salvo ML Ko TP Gandhi AK Goswami A Schirch V Safo MK 《Protein science : a publication of the Protein Society》2007,16(10):2184-2194
Pyridoxal kinase catalyzes the transfer of a phosphate group from ATP to the 5' alcohol of pyridoxine, pyridoxamine, and pyridoxal. In this work, kinetic studies were conducted to examine monovalent cation dependence of human pyridoxal kinase kinetic parameters. The results show that hPLK affinity for ATP and PL is increased manyfold in the presence of K(+) when compared to Na(+); however, the maximal activity of the Na(+) form of the enzyme is more than double the activity in the presence of K(+). Other monovalent cations, Li(+), Cs(+), and Rb(+) do not show significant activity. We have determined the crystal structure of hPLK in the unliganded form, and in complex with MgATP to 2.0 and 2.2 A resolution, respectively. Overall, the two structures show similar open conformation, and likely represent the catalytically idle state. The crystal structure of the MgATP complex also reveals Mg(2+) and Na(+) acting in tandem to anchor the ATP at the active site. Interestingly, the active site of hPLK acts as a sink to bind several molecules of MPD. The features of monovalent and divalent metal cation binding, active site structure, and vitamin B6 specificity are discussed in terms of the kinetic and structural studies, and are compared with those of the sheep and Escherichia coli enzymes. 相似文献
995.
Molecular architecture of DesV from Streptomyces venezuelae: a PLP-dependent transaminase involved in the biosynthesis of the unusual sugar desosamine 下载免费PDF全文
Burgie ES Thoden JB Holden HM 《Protein science : a publication of the Protein Society》2007,16(5):887-896
Desosamine is a 3-(dimethylamino)-3,4,6-trideoxyhexose found in certain macrolide antibiotics such as the commonly prescribed erythromycin. Six enzymes are required for its biosynthesis in Streptomyces venezuelae. The focus of this article is DesV, which catalyzes the PLP-dependent replacement of a 3-keto group with an amino functionality in the fifth step of the pathway. For this study the three-dimensional structures of both the internal aldimine and the ketimine intermediate with glutamate were determined to 2.05 A resolution. DesV is a homodimer with each subunit containing 12 alpha-helical regions and 12 beta-strands that together form three layers of sheet. The structure of the internal aldimine demonstrates that the PLP-cofactor is held in place by residues contributed from both subunits (Asp 164 and Gln 167 from Subunit I and Tyr 221 and Asn 235 from Subunit II). When the ketimine intermediate is present in the active site, the loop defined by Gln 225 to Ser 228 from Subunit II closes down upon the active site. The structure of DesV is similar to another sugar-modifying enzyme referred to as PseC. This enzyme is involved in the biosynthesis of pseudaminic acid, which is a sialic acid-like nonulosonate found in the flagellin of Helicobacter pylori. In the case of PseC, however, the amino group is transferred to the C-4 rather than the C-3 position. Details concerning the structural analysis of DesV and a comparison of its molecular architecture to that of PseC are presented. 相似文献
996.
Reticuline is a key compound in the biosynthetic pathway for isoquinoline alkaloids in plants, which include morphine, codeine
and berberine. We established cultured California poppy (Eschscholzia californica) cells, in which berberine bridge enzyme (BBE) was knocked down by RNA interference, to accumulate the important key intermediate
reticuline. Both BBE mRNA accumulation and enzyme activity were effectively suppressed in transgenic cells. In these transgenic
cells, end-products of isoquinoline alkaloid biosynthesis, such as sanguinarine, were considerably reduced and reticuline
was accumulated at a maximum level of 310 μg/g-fresh weight. In addition, 1 g-fresh weight of these cells secreted significant
amounts of reticuline into the medium, with a maximum level of 6 mg/20 mL culture medium. These cells also produced a methylated
derivative of reticuline, laudanine, which could scarcely be detected in control cells. We discuss the potential application
of RNAi technology in metabolic modification and the flexibility of plant secondary metabolism. 相似文献
997.
Jianbo Zhang Peng Ye Song Chen Weijing Wang 《International biodeterioration & biodegradation》2007,59(4):307-314
Researches on the polymerization of aqueous pentachlorophenol (PCP) by the catalysis of horseradish peroxidase (HRP) with the existence of hydrogen peroxide (H2O2) were conducted. Factors, such as acidity, temperature, enzyme activity, and initial concentration of PCP and H2O2 that could influence the degradation were studied. Results showed that the optimum pH value for free enzyme was 5–6; relative higher temperature could accelerate the reaction greatly; PCP removal increased with an increase of enzyme concentration, and PCP (initial concentration 12.6 mg/L) removal percentage could reach nearly 70% under the highest enzyme concentration (about 0.05 u/ml) adopted in the experiment; removal percentage increased slightly with an increase of initial concentration of PCP, and when initial PCP concentrations were 13.0 and 0.7 mg/L, the removal percentages were about 73.7% and 35.7%, respectively; the molar ratio of the reaction between PCP and H2O2 was about 1:2.Based on the above results, researches on the removal of PCP by the immobilized HRP were conducted. The free HRP was immobilized on the polyacrylamide gel prepared by gamma-ray radiation method; then the immobilized HRP was filled into a column, and PCP was successfully removed by the immobilized HRP column. The results were compared with results using free HRP enzyme, which showed that the optimum pH value for the immobilized HRP is similar to that for the free HRP, and when pH=5.15, the immobilized HRP could reduce PCP with initial concentration 13.4 mg/L to the concentration of 4.9 mg/L within 1 h, and the immobilized HRP column could be used to repeatedly. 相似文献
998.
Background
Implantable Cardioverter-defibrillators (ICD) reduce mortality in survivors of cardiac arrest (CA). We investigated the predictors of mortality after ICD implantation in survivors of CA.Methods
Retrospective review of clinical records and social security death index of all patients who received an ICD in a preexisting database of survivors of CA at the University of Pittsburgh Medical Center was performed. Multivariate analyses using the Cox proportional hazard model were performed with backward elimination to identify independent predictors of the time to death, and Kaplan-Meier curves were plotted.Results
Eighty patients (64 men) with a mean age of 64.4±12.5 years were followed for 4.7±2.3 years after ICD implantation. Survival rates were 93.8%, 65% and 50% at 1, 5, and 10 years, respectively. Independent predictors of time to death were determined to include age (hazard ratio (HR) = 1.91 per 10-year increase, p = 0.003), serum creatinine ≥ 1.3 mg/dL (HR = 2.56, p = 0.004), and QRS width >120 ms (HR = 5.14, p = 0.012).Conclusions
In this sample of ICD recipients secondary to CA, older age, elevated serum creatinine, and wider QRS duration were independent predictors of mortality. The presence of more than one risk factor in the same patient was associated with higher mortality rates. Whether interventions such as biventricular pacing can offset this increase risk of death warrants further investigation. 相似文献999.
Rosman J Dhillon S Mayer A Hanon S Paul S 《Indian pacing and electrophysiology journal》2007,7(4):215-217
Background
Cardiac Resynchronization Therapy (CRT) is indicated for the treatment of advanced heart failure with severe systolic dysfunction and intraventricular conduction delay. Patient selection for this technology is vital, though it remains unclear which patients benefit most from CRT. We tested the hypothesis that patients with non-ischemic cardiomyopathy have a superior mortality benefit from CRT than ischemic cardiomyopathy patients.Methods
We evaluated 95 CRT patients to determine which factors predict mortality.Results
Patients with non-ischemic cardiomyopathy had a significantly better prognosis than patients with ischemic cardiomyopathy.Conclusion
Larger prospective studies can substantiate this finding and better delineate which patients benefit most from CRT. 相似文献1000.
Sonia Ben Hadj Kalifa Ferid Limam M. Issam Smaali Thierry Maugard M. Nejib Marzouki 《World journal of microbiology & biotechnology》2007,23(10):1363-1370
The β-glucosidase enzyme β-glu2 isolated from Sclerotinia sclerotiorum was purified and used as tracer in enzyme linked immunosorbent assay. A novel purification procedure of the protein was developed
that consists of ammonium sulphate precipitation, gel filtration on Sephacryl S-200-HR column, ion exchange chromatography
on DEAE-Toyopearl and polybuffer exchanger PBE 94 TM chromatofocusing. The pI value was 4.45. K
m
and V
max values for the enzyme towards p-nitrophenyl-β-D-glucopyranoside were respectively 0.45 mM and 0.2 U/mL. Thermal stability showed that β-glu2 has a half-life
of 85 min at 55 °C and of 25 min at 65 °C. β-glu2 was conjugated to goat anti-rabbit antibodies with glutaraldehyde as cross
linking agent according to the one-step method. Conjugates were purified by HPLC gel filtration on TSK 2000. Enzymatic and
immunological activities of the β-glucosidase conjugate component were tested by the ELISA method. 相似文献