Structural and functional characterization of the human CCR5 receptor in complex with HIV gp120 envelope glycoprotein and CD4 receptor by molecular modeling studies

The entry of human immunodeficiency virus (HIV) into cells depends on a sequential interaction of the gp120 envelope glycoprotein with the cellular receptors CD4 and members of the chemokine receptor family. The CC chemokine receptor CCR5 is such a receptor for several chemokines and a major coreceptor for the entry of R5 HIV type-1 (HIV-1) into cells. Although many studies focus on the interaction of CCR5 with HIV-1, the corresponding interaction sites in CCR5 and gp120 have not been matched. Here we used an approach combining protein structure modeling, docking and molecular dynamics simulation to build a series of structural models of the CCR5 in complexes with gp120 and CD4. Interactions such as hydrogen bonds, salt bridges and van der Waals contacts between CCR5 and gp120 were investigated. Three snapshots of CCR5-gp120-CD4 models revealed that the initial interactions of CCR5 with gp120 are involved in the negatively charged N-terminus (Nt) region of CCR5 and positively charged bridging sheet region of gp120. Further interactions occurred between extracellular loop2 (ECL2) of CCR5 and the base of V3 loop regions of gp120. These interactions may induce the conformational changes in gp120 and lead to the final entry of HIV into the cell. These results not only strongly support the two-step gp120-CCR5 binding mechanism, but also rationalize extensive biological data about the role of CCR5 in HIV-1 gp120 binding and entry, and may guide efforts to design novel inhibitors.

Disconnection of the hippocampal-prefrontal cortical circuits impairs spatial working memory performance in rats

There is a unidirectional, ipsilateral and monosynaptic projection from the hippocampus to the prefrontal cortex. The cognitive function of hippocampal-prefrontal cortical circuit is not well established. In this paper, we use muscimol treated rats to inv

In vitro anti-HIV and -HSV activity and safety of sodium rutin sulfate as a microbicide candidate

Sodium rutin sulfate (SRS) is a sulfated rutin modified from the natural flavonol glycoside rutin. Here, we investigated its in vitro anti-HIV and -HSV activities and its cytotoxic profile. Fifty percent inhibitory concentration (IC50) values of SRS against HIV-1 X4 virus IIIB, HIV-1 R5 isolates Ada-M and Ba-L were 2.3 +/- 0.2, 4.5 +/- 2.0 and 8.5 +/- 3.8 mu M with a selectivity index (SI) of 563, 575 and 329, respectively. Its IC50 against primary R5 HIV-1 isolate from Yunnan province in China was 13.1 +/- 5.5 mu M, with a Sl of 197. In contrast, unsulfated rutin had no activity against any of the HIV-1 isolates tested. Further study indicated that SRS blocked viral entry and virus-cell fusion likely through interacting with the HIV- I envelope glycoprotein. SRS also demonstrated some activity against human herpes simplex virus (HSV) with an IC50 of 88.3 +/- 0.1 mu M and a Sl of 30. The 50% cytotoxicity concentration (CC50) of SRS was >3.0 mM, as determined in human genital ME 180, HeLa and primary human foreskin fibroblast cells. Minimum inhibitory concentration of SRS for vaginal lactobacilli was >3.0 mM. These results collectively indicate that SRS represents a novel candidate for anti-HIV-1/HSV microbicide development. (C) 2007 Elsevier B.V. All rights reserved.

长江上游龙溪河厚颌鲂种群资源的利用现状和保护

由于栖息地被破坏和过度捕捞等人为因素的影响,长江上游特有鱼类厚颌鲂M egalobrama pellegrini的种群资源显著减少。利用单位补充量模型进行分析,结果显示:长江上游支流龙溪河的厚颌鲂种群资源已经被过度开发,现有的捕捞强度(0.94年-1)远超过种群可承受的水平(F40%=0.18年-1,F0.1=0.20年-1和F25%=0.30年-1);繁殖潜力比为4.50%,低于25%,将造成种群的补充量不足,导致种群资源量下降;限制捕捞强度和捕捞规格是控制过度捕捞、保护种群资源的有效措施。

三峡库区浮游生物群落DNA结构与水体理化因子的分析

本文对三峡水库大坝至香溪河段所设A、B、C、D、E、F和G等7个站点浮游生物群落DNA进行了RAPD分子生物学研究,并分析了其与水体理化因子的关系。各站点间RAPD研究表明:D和E首先聚到一组,然后与A聚到一起,最后与C聚成一大类;B和F聚成一大类;站点G独自归于一类。而理化因子聚类结果显示:B首先与C聚为一小类,再与D聚到一起,然后与G、F聚成的小类聚为一类,而E与A分别单独归为一类。比较发现,RAPD聚类结果中相距较近的站点在理化因子聚类中显示为相距较远的站点(如站点A、C、D、E之间),而在RAPD