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881.
Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain 总被引:34,自引:0,他引:34
Liu Z Sun C Olejniczak ET Meadows RP Betz SF Oost T Herrmann J Wu JC Fesik SW 《Nature》2000,408(6815):1004-1008
The inhibitor-of-apoptosis proteins (IAPs) regulate programmed cell death by inhibiting members of the caspase family of enzymes. Recently, a mammalian protein called Smac (also named DIABLO) was identified that binds to the IAPs and promotes caspase activation. Although undefined in the X-ray structure, the amino-terminal residues of Smac are critical for its function. To understand the structural basis for molecular recognition between Smac and the IAPs, we determined the solution structure of the BIR3 domain of X-linked IAP (XIAP) complexed with a functionally active nine-residue peptide derived from the N terminus of Smac. The peptide binds across the third beta-strand of the BIR3 domain in an extended conformation with only the first four residues contacting the protein. The complex is stabilized by four intermolecular hydrogen bonds, an electrostatic interaction involving the N terminus of the peptide, and several hydrophobic interactions. This structural information, along with the binding data from BIR3 and Smac peptide mutants reported here, should aid in the design of small molecules that may be used for the treatment of cancers that overexpress IAPs. 相似文献
882.
Mutations in the gene encoding ABCR (ABCA4), a photoreceptor-specific ATP-binding cassette (ABC) transporter, are responsible for autosomal recessive Stargardt disease (STGD), an early onset macular degeneration, and some forms of autosomal recessive cone-rod dystrophy and autosomal recessive retinitis pigmentosa. Heterozygosity for ABCA4 mutations may also represent a risk factor for age-related macular degeneration (AMD), although this idea is controversial. An ongoing challenge in the analysis of ABCA4-based retinopathies arises from the observation that most of the ABCA4 sequence variants identified so far are missense mutations that are rare in both patient and control populations. With the current sample size of most sequence variants, one cannot determine statistically whether a particular sequence variant is pathogenic or neutral. A related challenge is to determine the degree to which each pathogenic variant impairs ABCR function, as genotype-phenotype analyses indicate that age of onset and disease severity correlate with different ABCA4 alleles. To address these questions, we performed a functional analysis of human ABCR and its variants. These experiments reveal a wide spectrum of biochemical defects in these variants and provide insight into the transport mechanism of ABCR. 相似文献
883.
运用牛顿动力学方法对单级倒立摆系统进行了数学建模,并对基于经典控制理论的PID控制法、基于自适应神经网络模糊控制方法进行了仿真对比分析研究。 相似文献
884.
885.
本文通过建立概率模型,分别运用完备事件组、全概率公式及随机变量的数字特征等方法,举例证明了几类组合恒等式;既是概率论在证明组合恒等式方面的广泛应用,又充分展现了概率证法的独到之处。 相似文献
886.
A 4 Mb embedded silicon-oxide-nitride-oxide-silicon (SONOS) memory was developed with a 0.18 μm CMOS logic compatible technology. A reverse programming array architecture was proposed to reduce the chip area, enhance the operating window, and increase the read speed. The charge distribution was analyzed to optimize the programming and erase conditions considering both the operating speed and the endurance performance. The final test chip has a good endurance of 105 cycles and a data retention time of at least 10 years. 相似文献
887.
WANG YongSheng SUN HongMei TAO XuePing SHEN Qi ZHANG Yong 《科学通报(英文版)》2007,52(23):3193-3199
The reaction of anhydrous FeBr2 with two equivalents of anionic N-heterocyclic carbene (NaL1 and NaL2), which are generated in situ by the reaction of the corresponding salt [4-R-C6H4COCH2{CH- (NCHCHNiPr)}Br] (R = OCH3, H2L1Br, 1; R = F, H2L2Br, 2) with two equivalents of NaN(SiMe3)2, affords bis-ligand Fe(II) complexes of L12Fe (3) and L22Fe (4) in high yield, respectively. Attempt to synthesize mono-ligand Fe(II) bromide by the 1:1 molar ratio of NaL to FeBr2 is unsuccessful, and the same com- plexes of 3 and 4 were obtained. Both 3 and 4 have been depicted by elemental analysis and X-ray structure determination. Preliminary studies show that both 3 and 4 can be used as single-component catalyst for the ring-opening polymerization of ε-caprolactone, and the catalytic activity of 3 is higher than that of 4. 相似文献
888.
引入一类相关负风险和风险过程,负风险和类之间的相关性定义为稀疏相关结构,主要研究类之间的相关性对破产概率的影响. 相似文献
889.
研制了150kHz中频交流脉冲电源,给出了中频交流脉冲电源的设计思路和实现方案.该电源采用全桥逆变拓朴电路、PWM控制方式、输出功率叠加的方案,具有输出变压器原边平均电流和副边峰值电流的过流保护功能.其输出峰值电压0~1200V连续可调,频率1~150kH z可调,脉宽占空比10%~40%可调,输出平均电流0~5A,最大输出功率5kW.利用该电源进行了等离子体化学气相沉积和反应溅射实验,证明该电源各项指标运行正常,工作稳定,具有良好的应用价值. 相似文献
890.
孙仁斌 《中南民族大学学报(自然科学版)》2007,26(1):94-96
在半空间上讨论了一类退缩抛物型方程组解的存在性与爆破性质.证明了当初值较大时解会在有限时刻发生爆破,而当初值适当小时,解具有全局存在性. 相似文献