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46 条记录 (耗时 0.045 秒)

    Crystal structure of WW domains and methods of use thereof
    5.
    发明授权
    Crystal structure of WW domains and methods of use thereof 有权
    WW域的晶体结构及其使用方法

    公开(公告)号：US07127357B1

    公开(公告)日：2006-10-24

    申请号：US09733773

    申请日：2000-12-08

    申请人： Joseph P. Noel ,  Mark A. Verdecia

    发明人： Joseph P. Noel ,  Mark A. Verdecia

    IPC分类号： G06N3/00 ,  G06N7/00 ,  G06G7/58

    CPC分类号： G06F19/16 ,  G06F19/18

    摘要： A WW domain crystal structure of Pin1 is provided. In addition, methods of using the crystal structure and atomic coordinates for the development of WW domain binding agents is also provided. Also provided are computer programs on computer readable medium for use in developing WW domain binding agents.

    摘要翻译： 提供了Pin1的WW域晶体结构。 此外，还提供了使用晶体结构和原子坐标来开发WW结构域结合剂的方法。 还提供了用于开发WW域结合剂的计算机可读介质上的计算机程序。

    Structure of the farnesoid X receptor ligand binding domain and methods of use therefor
    6.
    发明授权
    Structure of the farnesoid X receptor ligand binding domain and methods of use therefor 失效
    法呢酯X受体配体结合域的结构及其用途

    公开(公告)号：US08212006B2

    公开(公告)日：2012-07-03

    申请号：US12686347

    申请日：2010-01-12

    申请人： Michael R. Downes ,  Mark A. Verdicia ,  Joseph P. Noel ,  Ronald M. Evans ,  Lindsey J. Bowman ,  Marianne Bowman

    发明人： Michael R. Downes ,  Mark A. Verdicia ,  Joseph P. Noel ,  Ronald M. Evans ,  Lindsey J. Bowman ,  Marianne Bowman

    IPC分类号： C07K1/00 ,  G06G7/58 ,  A01N61/00

    CPC分类号： C07K14/70567 ,  C07K2299/00 ,  G01N33/743 ,  G01N2500/00 ,  G06F19/16 ,  G06F19/706

    摘要： The present invention provides compositions comprising the ligand binding domain (LBD) of a farnesoid X receptor (FXR) in crystalline form. In alternative embodiments, the LBD of FXR is complexed with a ligand therefor. There are provided high resolution structures of FXR complexed with a novel high affinity agonist fexaramine. The discovered structure of a FXR LBD provides the first three-dimensional view of the structural basis for FXR ligand binding. The present invention further provides a computer for producing a time-dimensional representation of FXR or a complex thereof, and a computer for determining at least a portion of the structure coordinates of FXR or a complex thereof. The present invention further provides methods of using this structural information to predict molecules capable of binding to FXR; to identify compounds with agonist, antagonist or partial agonist activity for FXR; and to determine whether a test compound is capable of binding to the LBD of FXR. The present invention further provides compositions comprising compounds identified by such invention methods.

    摘要翻译： 本发明提供了包含结晶形式的法呢甾X受体（FXR）的配体结合结构域（LBD）的组合物。 在替代实施方案中，FXR的LBD与其配体复合。 提供了与新型高亲和力激动剂福沙康胺复合的FXR的高分辨率结构。 所发现的FXR LBD的结构提供了FXR配体结合的结构基础的第一个三维视图。 本发明还提供一种用于产生FXR或其复数的时间维度表示的计算机，以及用于确定FXR或其复数的结构坐标的至少一部分的计算机。 本发明还提供使用该结构信息来预测能够结合FXR的分子的方法; 识别FXR激动剂，拮抗剂或部分激动剂活性的化合物; 并确定测试化合物是否能够结合FXR的LBD。 本发明还提供包含通过本发明方法鉴定的化合物的组合物。

    NOVEL AROMATIC PRENYLTRANSFERASES, NUCLEIC ACIDS ENCODING SAME AND USES THEREFOR
    10.
    发明申请
    NOVEL AROMATIC PRENYLTRANSFERASES, NUCLEIC ACIDS ENCODING SAME AND USES THEREFOR 有权
    新型芳香丙烯酸酯，编码其的核酸及其用途

    公开(公告)号：US20100285502A1

    公开(公告)日：2010-11-11

    申请号：US12480618

    申请日：2009-06-08

    申请人： Tomohisa Kuzuyama ,  Joseph P. Noel ,  Stephane P. Richard

    发明人： Tomohisa Kuzuyama ,  Joseph P. Noel ,  Stephane P. Richard

    IPC分类号： G01N33/573 ,  C12P21/06 ,  C12N9/10 ,  C07H21/04

    CPC分类号： C12N9/1085

    摘要： In accordance with the present invention, a novel aromatic prenyltransferase, Orf2 from Streptomyces sp. strain CL190, involved in naphterpin biosynthesis has been identified and the structure thereof elucidated. This prenyltransferase catalyzes the formation of a C—C bond between a prenyl group and a compound containing an aromatic nucleus, and also displays C—O bond formation activity. Numerous crystallographic structures of the prenyltransferase have been solved and refined, e.g., (1) prenyltransferase complexed with a buffer molecule (TAPS), (2) prenyltransferase as a binary complex with geranyl diphosphate (GPP) and Mg2+, and prenyltransferase as ternary complexes with a non-hydrolyzable substrate analogue, geranyl S-thiolodiphosphate (GSPP) and either (3) 1,6-dihydroxynaphthalene (1,6-DHN), or (4) flaviolin (i.e., 2,5,7-trihydroxy-1,4-naphthoquinone, which is the oxidized product of 1,3,6,8-tetrahydroxynaphthalene (THN)). These structures have been solved and refined to 1.5 Å, 2.25 Å, 1.95 Å and 2.02 Å, respectively. This first structure of an aromatic prenyltransferase displays an unexpected and non-canonical (β/α)-barrel architecture. The complexes with both aromatic substrates and prenyl containing substrates and analogs delineate the active site and are consistent with a proposed electrophilic mechanism of prenyl group transfer. These structures also provide a mechanistic basis for understanding prenyl chain length determination and aromatic co-substrate recognition in this structurally unique family of aromatic prenyltransferases. This structural information is useful for predicting the aromatic prenyltransferase activity of proteins.

    摘要翻译： 根据本发明，一种新型芳族异戊烯基转移酶，来自链霉菌属的Orf2。 已经鉴定了参与萘普生生物合成的菌株CL190，其结构被阐明。 该异戊烯基转移酶催化异戊烯基和含有芳香核的化合物之间的C-C键的形成，并且还显示C-O键的形成活性。 已经解决和改进了异戊烯基转移酶的许多晶体结构，例如（1）与缓冲分子（TAPS）复合的异戊烯基转移酶，（2）作为二进位配合物的前体甲基转移酶与香叶基二磷酸（GPP）和Mg2 +以及异戊烯基转移酶作为三元复合物 不可水解的底物类似物，香叶基S-硫代双磷酸（GSPP）和（3）1,6-二羟基萘（1,6-DHN）或（4）黄堇素（即2,5,7-三羟基-1， 4-萘醌，其为1,3,6,8-四羟基萘（THN）的氧化产物）。 这些结构分别被解析和精炼成1.5A，2.25，1.95和2.02。 芳香族异戊烯基转移酶的这种第一种结构显示出意想不到的和非规范的（＆bgr。/α） - 桶结构。 具有芳香底物和含异戊烯基的底物和类似物的络合物描绘了活性位点，并与提出的异戊烯基转移的亲电子机制一致。 这些结构还提供了在这个结构独特的芳族异戊烯基转移酶家族中了解异戊烯基链长度测定和芳香族共底物识别的机理基础。 该结构信息对于预测蛋白质的芳族异戊烯基转移酶活性是有用的。