Hepatitis C virus NS3 helicase subdomain I
    1.
    发明授权
    Hepatitis C virus NS3 helicase subdomain I 失效
    丙型肝炎病毒NS3解旋酶子域I

    公开(公告)号:US07459296B2

    公开(公告)日:2008-12-02

    申请号:US09825423

    申请日:2001-04-03

    IPC分类号: C12N9/12 C07K14/00 G01N31/00

    摘要: This invention provides fragments of HCV NS3 helicase, and crystalline compositions thereof, based on subdomains of HCV helicase protein. The protein fragments are stable, soluble, and structurally sound. They can be expressed at high levels in conventional expressions systems, such as E. coli, to permit efficient, large-scale production for NMR-based screening applications and production of [2H,13C,15N]- and [13C,15N]-labeled polypeptides for structural NMR studies. Helicase fragments of the present invention are useful in the most advanced NMR techniques available, e.g., NMR-based drug discovery techniques such as SAR-by-NMR, in biological assays to discover inhibitors of HCV NS3 helicase, and to evaluate the mechanism of action and substrates for HCV NS3 helicase. Crystals of the present invention are useful for structure-based drug design studies using x-ray crystallographic techniques.

    摘要翻译: 本发明基于HCV解旋酶蛋白的亚结构域提供HCV NS3解旋酶的片段及其结晶组合物。 蛋白质片段稳定,可溶,结构合理。 它们可以在常规表达系统如大肠杆菌中以高水平表达,以允许基于NMR的筛选应用的有效的大规模生产和[2H,13C,15N] - 和[13C,15N] - 用于结构NMR研究的标记多肽。 本发明的螺旋酶片段可用于可用的最先进的NMR技术,例如基于NMR的药物发现技术,例如通过核磁共振的核磁共振(NMR),用于发现HCV NS3解旋酶抑制剂的生物测定中,以及评估作用机制 和HCV NS3解旋酶的底物。 本发明的晶体可用于使用x射线晶体学技术的基于结构的药物设计研究。

    Crystalline form of an n231 mutant catalytic domain of ADAM33 and methods of use thereof
    4.
    发明授权
    Crystalline form of an n231 mutant catalytic domain of ADAM33 and methods of use thereof 失效
    ADAM33的n231突变体催化结构域的结晶形式及其使用方法

    公开(公告)号:US07285408B2

    公开(公告)日:2007-10-23

    申请号:US10741208

    申请日:2003-12-19

    IPC分类号: C12N9/50 C12N9/00 G01N31/00

    摘要: The present invention discloses purified polypeptides that comprise an active human ADAM33 catalytic domain. In addition, the present invention discloses nucleic acids that encode the polypeptides of the present invention. The present invention also discloses methods of growing X-ray diffractable crystals of polypeptides comprising the active human ADAM33 catalytic domain. The present invention further discloses a crystalline form of a catalytic domain of human ADAM33. In addition, the present invention discloses methods of using the X-ray diffractable crystals of human ADAM33 in structure based drug design to identify compounds that can modulate the enzymatic activity of human ADAM33. The present invention also discloses methods of treating respiratory disorders by administering therapeutic amounts of the human ADAMS33 catalytic domain.

    摘要翻译: 本发明公开了包含活性人ADAM33催化结构域的纯化多肽。 此外,本发明公开了编码本发明多肽的核酸。 本发明还公开了生长包含活性人ADAM33催化结构域的多肽的X射线衍射晶体的方法。 本发明还公开了人ADAM33的催化结构域的结晶形式。 此外,本发明公开了在基于结构的药物设计中使用人ADAM33的X射线衍射晶体的方法来鉴定可以调节人ADAM33的酶活性的化合物。 本发明还公开了通过施用治疗量的人ADAMS33催化结构域来治疗呼吸系统疾病的方法。