Crystalline form of an n231 mutant catalytic domain of ADAM33 and methods of use thereof
    7.
    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。

    Method for making β-secretase co-crystals complexed with a ligand
    8.
    发明授权
    Method for making β-secretase co-crystals complexed with a ligand 有权
    制备与配体络合的β-分泌酶共晶体的方法

    公开(公告)号:US07569391B2

    公开(公告)日:2009-08-04

    申请号:US11634737

    申请日:2006-12-06

    IPC分类号: G01N31/00 G01N33/00

    CPC分类号: C12N9/6421 C07K2299/00

    摘要: The present application relates to methods for growing crystals of both the uncomplexed and complexed forms of β-secretase (BACE) polypeptide. The present application also relates to crystalline forms of uncomplexed BACE and the three-dimensional structure of BACE, as determined from the crystals. In addition, the present application relates to the use of crystalline forms of BACE to identify ligands, preferably inhibitors (antagonists), which bind to, and preferably inhibit the enzymatic activity of, BACE. Furthermore, the present application relates to nucleic acid sequences encoding human BACE polypeptide, and methods for making BACE in greater quantity than prior methods, resulting in more effective crystallization.

    摘要翻译: 本申请涉及用于生长未络合和复合形式的β-分泌酶(BACE)多肽的晶体的方法。 本申请还涉及未结合的BACE的晶体形式和由晶体确定的BACE的三维结构。 此外,本申请涉及BACE的结晶形式用于鉴定与BACE结合并优选抑制BACE的酶活性的配体,优选抑制剂(拮抗剂)。 此外,本申请涉及编码人BACE多肽的核酸序列和与以前的方法相比制备BACE的方法,导致更有效的结晶。

    Refolded recombinant β-secretase crystals and methods for preparing and using the same
    9.
    发明授权
    Refolded recombinant β-secretase crystals and methods for preparing and using the same 有权
    重折叠重组和分泌酶晶体及其制备和使用方法

    公开(公告)号:US08063185B2

    公开(公告)日:2011-11-22

    申请号:US12434897

    申请日:2009-05-04

    IPC分类号: C12N1/12

    CPC分类号: C12N9/6421 C07K2299/00

    摘要: The present application relates to methods for growing crystals of both the uncomplexed and complexed forms of β-secretase (BACE) polypeptide. The present application also relates to crystalline forms of uncomplexed BACE and the three-dimensional structure of BACE, as determined from the crystals. In addition, the present application relates to the use of crystalline forms of BACE to identify ligands, preferably inhibitors (antagonists), which bind to, and preferably inhibit the enzymatic activity of, BACE. Furthermore, the present application relates to nucleic acid sequences encoding BACE polypeptide, and methods for making BACE in greater quantity than prior methods, resulting in more effective crystallization.

    摘要翻译: 本申请涉及用于生长未络合和复合形式的分泌型(BACE)多肽的晶体的方法。 本申请还涉及未结合的BACE的晶体形式和由晶体确定的BACE的三维结构。 此外,本申请涉及BACE的结晶形式用于鉴定与BACE结合并优选抑制BACE的酶活性的配体,优选抑制剂(拮抗剂)。 此外,本申请涉及编码BACE多肽的核酸序列和与以前的方法相比制备BACE的方法,导致更有效的结晶。

    Refolded recombinant beta-secretase crystals and methods for preparing and using the same
    10.
    发明申请
    Refolded recombinant beta-secretase crystals and methods for preparing and using the same 有权
    重折叠重组β-分泌酶晶体及其制备和使用方法

    公开(公告)号:US20070099273A1

    公开(公告)日:2007-05-03

    申请号:US11634737

    申请日:2006-12-06

    IPC分类号: G06F19/00 C12P21/06 C12N9/64

    CPC分类号: C12N9/6421 C07K2299/00

    摘要: The present application relates to methods for growing crystals of both the uncomplexed and complexed forms of β-secretase (BACE) polypeptide. The present application also relates to crystalline forms of uncomplexed BACE and the three-dimensional structure of BACE, as determined from the crystals. In addition, the present application relates to the use of crystalline forms of BACE to identify ligands, preferably inhibitors (antagonists), which bind to, and preferably inhibit the enzymatic activity of, BACE. Furthermore, the present application relates to nucleic acid sequences encoding BACE polypeptide, and methods for making BACE in greater quantity than prior methods, resulting in more effective crystallization.

    摘要翻译: 本申请涉及用于生长未络合和复合形式的β-分泌酶(BACE)多肽的晶体的方法。 本申请还涉及未结合的BACE的晶体形式和由晶体确定的BACE的三维结构。 此外,本申请涉及BACE的结晶形式用于鉴定与BACE结合并优选抑制BACE的酶活性的配体,优选抑制剂(拮抗剂)。 此外,本申请涉及编码BACE多肽的核酸序列和与以前的方法相比制备BACE的方法,导致更有效的结晶。