Molecular modeling on human CCR5 receptors and complex with CD4 antigens and HIV-1 envelope glycoprotein gp120

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	Molecular modeling on human CCR5 receptors and complex with CD4 antigens and HIV-1 envelope glycoprotein gp120
	Yang J 1; Liu CQ[*]1,2
刊名	ACTA PHARMACOLOGICA SINICA
	2000
卷号	21 期号:1 页码:29-34
关键词	CCR5 receptors CD4 antigens HIV envelope protein HIV-1 chemokine receptors HLA antigens molecular models
ISSN号	0253-9756
其他题名	人CCR5受体与CD4抗原和HIV-1包膜糖蛋白gp120复合物的分子模型
通讯作者	jfhuang@public.km.yn.cn
合作状况	其它
中文摘要	目的:研究人CCR5与CD4抗原和HIV-1包膜糖蛋白gp120的相互作用。方法:人CCR5受体的结构保守区由SYBYL软件中的Biopolymer模块建立,非保守区由LOOP SEARCH方法建立。将得到的结构模型与CD4抗原和gp120结合形成复合物。结果:人CCR5受体既可以与CD4抗原相互作用,也可以和gp120相互作用,其N-末端残基通过静电和氢键方式与CD4相互作用,并深埋在一个疏水中心里,被碱性基团包围。而且有7个氨基酸残基通过范德华作用、疏水性作用和氢键与6个gp120残基相互作用。结论:该模型将有助于设计作用更强的抗艾滋病药物。
英文摘要	AIM: To investigate the interaction between human CCR5 receptors (CCR5) and HIV-1 envelope glycoprotein gp120 (HIV-1 gp120) and HIV-1 receptor CD4 antigens (CD4). METHODS: The structurally con served regions (SCR) of human CCR5 was built by the SYBYL/Biopolymer module using the corresponding transmembrane (TM) domain of bacteriorhodopsin (bR) as the template. The coordinates for amino-ter minal residue sequence, and carboxyl-terminal residue sequence, extracellular and cytoplasmic loops were generated using LOOP SEARCH algorithm. Subsequently the structural model was merged into the complex with HIV-1 gp120 and CD4. RESULTS: Human CCR5 interacted with both an HIV-1 gp120 and CD4. The N-terminal residues (especially Met1 and Gln4) of human CCR5, contacted with CD4 residues, mainly 7Nith one span (56 - 59) of CD4 in electrostatic interaction and hydrogen-bonds. The binding sites of human CCR5 were buried in a hydrophobic center surrounded by a highly basic periphery. On the other hand, direct interatomic contacts were made between ? CCR5 residues and 6 gp120 amino-acid residues, which included van der Waals contacts, hydrophobic interaction, and hydrogen bonds. CONCLUSION: The interaction model should be helpful for rational design of novel anti-HIV drugs.
收录类别	SCI
资助信息	Project supported by the National Natural Science Foundation of China, № 39770418.
原文出处	20002129.pdf
语种	英语
公开日期	2010-08-24
内容类型	期刊论文
源URL	[http://159.226.149.42:8088/handle/152453/5181]
专题	昆明动物研究所_其他昆明动物研究所_细胞与分子进化开放实验室
作者单位	1.Chinese Acad Sci, Kunming Inst Zool, Lab Cellular & Mol Evolut, Kunming 650223, Peoples R China 2.Yunnan Univ, Modern Biol Ctr, Kunming 650091, Peoples R China
推荐引用方式 GB/T 7714	Yang J,Liu CQ[*]. Molecular modeling on human CCR5 receptors and complex with CD4 antigens and HIV-1 envelope glycoprotein gp120[J]. ACTA PHARMACOLOGICA SINICA,2000,21(1):29-34.
APA	Yang J,&Liu CQ[*].(2000).Molecular modeling on human CCR5 receptors and complex with CD4 antigens and HIV-1 envelope glycoprotein gp120.ACTA PHARMACOLOGICA SINICA,21(1),29-34.
MLA	Yang J,et al."Molecular modeling on human CCR5 receptors and complex with CD4 antigens and HIV-1 envelope glycoprotein gp120".ACTA PHARMACOLOGICA SINICA 21.1(2000):29-34.