Structure of the human histamine H1 receptor complex with doxepin

The biogenic amine histamine is an important pharmacological mediator involved in pathophysiological processes such as allergies and inflammations. Histamine H(1) receptor (H(1)R) antagonists are very effective drugs alleviating the symptoms of allergic reactions. Here we show the crystal structure of the H(1)R complex with doxepin, a first-generation H(1)R antagonist. Doxepin sits deep in the ligand-binding pocket and directly interacts with Trp?428(6.48), a highly conserved key residue in G-protein-coupled-receptor activation. This well-conserved pocket with mostly hydrophobic nature contributes to the low selectivity of the first-generation compounds. The pocket is associated with an anion-binding region occupied by a phosphate ion. Docking of various second-generation H(1)R antagonists reveals that the unique carboxyl group present in this class of compounds interacts with Lys?191(5.39) and/or Lys?179(ECL2), both of which form part of the anion-binding region. This region is not conserved in other aminergic receptors, demonstrating how minor differences in receptors lead to pronounced selectivity differences with small molecules. Our study sheds light on the molecular basis of H(1)R antagonist specificity against H(1)R.     

Structural insight into brassinosteroid perception by BRI1

Brassinosteroids are essential phytohormones that have crucial roles in plant growth and development. Perception of brassinosteroids requires an active complex of BRASSINOSTEROID-INSENSITIVE 1 (BRI1) and BRI1-ASSOCIATED KINASE 1 (BAK1). Recognized by the extracellular leucine-rich repeat (LRR) domain of BRI1, brassinosteroids induce a phosphorylation-mediated cascade to regulate gene expression. Here we present the crystal structures of BRI1(LRR) in free and brassinolide-bound forms. BRI1(LRR) exists as a monomer in crystals and solution independent of brassinolide. It comprises a helical solenoid structure that accommodates a separate insertion domain at its concave surface. Sandwiched between them, brassinolide binds to a hydrophobicity-dominating surface groove on BRI1(LRR). Brassinolide recognition by BRI1(LRR) is through an induced-fit mechanism involving stabilization of two interdomain loops that creates a pronounced non-polar surface groove for the hormone binding. Together, our results define the molecular mechanisms by which BRI1 recognizes brassinosteroids and provide insight into brassinosteroid-induced BRI1 activation.     

四膜虫有性生殖过程中特异表达基因TCD3的序列分析

含有CHROMO(chromatin organization modifier)结构域的蛋白参与了染色质结构的调节.本研究从嗜热四膜虫(Tetrahymena thermophila)全基因数据库(www.ciliate.org)和基因表达数据库(tged.ihb.ac.cn)中筛选到有性生殖特异表达TCD3(Tetrahymena chromo domain-containing protein 3)基因.该基因ORF为1 005bp,大核染色体中基因全长1 241bp,含有两个内含子.5′-RACE和3′-RACE表明5′端非编码区(5′-UTR)长度为40bp,3′端非编码区(3′-UTR)长度为90bp.TCD3基因预测编码334个氨基酸构成,含有一个CHROMO结构域.CHROMO结构域聚类分析表明四膜虫Tcd3蛋白可能与线虫CeCDP功能类似,参与异染色质的形成和DNA序列删除.     

高职院校ASP.NET程序设计教学改革与思考

ASP.NET程序设计是一门实践性极强的职业技能型课程,在计算机专业课中处于非常重要的地位.文章分析了高职ASP.NET程序设计课程的教学现状及存在的问题,总结提出大案例贯穿——做中学教学设计思路,将工业制造过程(毛胚—成品—精品)运用于程序设计教学过程,培养学生做学一体的学习意识,提高其自学能力,并在教学过程中进行实践检验,对出现的问题进行了有益探索与思考.     

火灾救援中的最优资源分配方案

随着近年来灾情发生越来越频繁,关于灾情中最优资源分配的研究也越来越多,但现有研究没能把各种救援资源分配和灾情现场情况、社会总损失等结合起来考虑.本文以动态灾情救援Pareto最优(即社会总损失最小)为目标,考虑了救援力量不能提供有效资源造成的损失、资源传输过程中存在的损失以及灾情现场造成的损失等三种损失因素,给出了一个...     

化合物LaCo2Al8的晶体结构及其Rietveld精修

利用X射线粉末衍射技术和Rietveld结构修正方法对LaCo2Al8进行了研究,结果表明,化合物LaCo2Al8具有正交CaCo2Al8结构类型,空间群为Pbam(№.55),点阵参数为α=1.252 711(4)nm,b=1.441 71(5)nm,c=0.404 22(1)nm,指标化的可靠性因子为152.0(4...     

欧拉和的新证明

借助类比的数学思想,利用根与系数的关系及函数项级数一致收敛的概念,给出欧拉和的几种新的证明方法.     

双二茂铁基醇与甲苯二异氰酸酯合成聚氨酯及其性质研究

将含有双二茂铁基的二元仲酵与甲苯二异氰酸酯反应,合成相应的聚氨酯,研究了反应时间对反应产物分子量的影响.通过元素分析、红外光谱、核磁共振对聚合物的结构进行表征,用凝胶渗透色谱(GPC)测定了聚合物的分子量,用差热-热重(DTA-TGA)研究了聚合物的热性能,用循环伏安法测定了聚合物的氧化还原性质.研究结果表明,含双二茂铁基聚氨酯的热稳定性比没有引入双二茂铁基的聚氨酯有明显提高,与双二茂铁基丙烷相比,其在相同电化学反应条件下更易被氧化.     

植物miRNAs前体的生物信息分析

miRNAs前体（premiRNAs）是产生成熟miRNAs的基因表达产物,能形成较为稳定的发卡环结构,具有较低的最小折叠自由能（minimal folding free energy,MFE）。在对植物premiRNAs长度、不同碱基含量、MFE、熵分析基础上,重点比较不同RNAs序列之间MFE与其长度的比值（MFEL）。结果表明MFEL是区分植物premiRNAs的一个很有效的参数：premiRNAs的MFEL值平均为45.98 kcal/mol,明显低于mRNAs（23.08 kcal/     

动态心电监护仪中心电信号采集与无线收发系统的设计

设计一个基于无线的心电信号采集与收发系统,从而实现动态心电监护仪中信号采集部分与信号分析处 理部分的分离,克服了随着设备功能越来越强大而带来的体积质量增大引起的用户佩戴不便的缺点,也增强了设 备应用的灵活性。