國家衛生研究院 NHRI:Item 3990099045/11777
English  |  正體中文  |  简体中文  |  全文笔数/总笔数 : 12145/12927 (94%)
造访人次 : 852160      在线人数 : 1394
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜寻范围 查询小技巧：
  • 您可在西文检索词汇前后加上"双引号"，以获取较精准的检索结果
  • 若欲以作者姓名搜寻，建议至进阶搜寻限定作者字段，可获得较完整数据
    •  进阶搜寻
    主页 ‧ 登入 ‧ 上传 ‧ 说明 ‧ 关于NHRI ‧ 管理 到手机版


    jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/11777


    题名: Characterization, dynamics, and mechanism of CXCR4 antagonists on a constitutively active mutant
    作者: Rosenberg, EM, Jr.;Harrison, RES;Tsou, LK;Drucker, N;Humphries, B;Rajasekaran, D;Luker, KE;Wu, CH;Song, JS;Wang, CJ;Murphy, JW;Cheng, YC;Shia, KS;Luker, GD;Morikis, D;Lolis, EJ
    贡献者: Institute of Biotechnology and Pharmaceutical Research
    摘要: The G protein-coupled receptor (GPCR) CXCR4 is a co-receptor for HIV and is involved in cancers and autoimmune diseases. We characterized five purine or quinazoline core polyamine pharmacophores used for targeting CXCR4 dysregulation in diseases. All were neutral antagonists for wild-type CXCR4 and two were biased antagonists with effects on beta-arrestin-2 only at high concentrations. These compounds displayed various activities for a constitutively active mutant (CAM). We use the IT1t-CXCR4 crystal structure and molecular dynamics (MD) simulations to develop two hypotheses for the activation of the N119(3.35)A CAM. The N119(3.35)A mutation facilitates increased coupling of TM helices III and VI. IT1t deactivates the CAM by disrupting the coupling between TM helices III and VI, mediated primarily by residue F87(2.53). Mutants of F87(2.53) in N119(3.35)A CXCR4 precluded constitutive signaling and prevented inverse agonism. This work characterizes CXCR4 ligands and provides a mechanism for N119(3.35)A constitutive activation.
    日期: 2019-05
    關聯: Cell Chemical Biology. 2019 May;26(5):662-673.e7.
    Link to: http://dx.doi.org/10.1016/j.chembiol.2019.01.012
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2451-9448&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000468134800009
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85065487326
    显示于类别:[鄒倫] 期刊論文
    [夏克山] 期刊論文

    文件中的档案:

    档案 描述 大小格式浏览次数
    PUB30827936.pdf3459KbAdobe PDF417检视/开启


    在NHRI中所有的数据项都受到原著作权保护.

    TAIR相关文章

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回馈