STRUCTURAL DETERMINATION OF CATALYTIC DOMAIN OF PTP1: TUMOR SUPPRESSOR GENE

PTP1C属于SH2-PTP家族，是一种蛋白质 N端含有两个SH2结构域的酪氨酸磷酸酶。 PTP1C作为负性调节器参与了 造血细胞的分化。它也是肿瘤 抑癌基因参与白血病、卵巢癌等癌症的发生。 在这份提案中，我们正在申请同步加速器的时间来收集 一组高分辨率的原生数据，来自 PTP1C的催化结构域。晶体的尺寸为0.1x0.1x 0.1mm3。它将衍变到3.0零下160摄氏度，使用RAXIS-II机器 在华盛顿大学马萨诸塞州医疗中心。空间群是C222，有两个 不对称单元中的分子。单元格尺寸为a= 117.048，b=132.649，c=134.989。然而，重新合并的 衍射数据为15%。因此，我们正在申请 同步加速器收集一组高分辨率本机数据的时间为 国际象棋。我们打算用分子来解决结构问题 取代法，以PTP1B的晶体结构为基础 搜索模型。PTP1B和PTP1C的序列同源性为35%。 如有需要，我们会使用 加州大学马萨诸塞州医疗中心的RAXIS机器。

PTP1C belongs to a family called SH2-PTP, which are protein tyrosine phosphatases containing two SH2 domains at their N-terminals. PTP1C behaves as the negative regulator involved in the differentiation of hematopoietic cells. It is also the tumor suppressor gene involved in leukemia, ovary cancer and other cancers. In this proposal, we are applying for the synchrotron time to collect a set of high resolution native data, from the crystals of the catalytic domain of PTP1C. The crystals have the sizes of 0.1 x 0.1 x 0.1 mm3. It diffracts to 3.0
at -160oC, using the RAXIS-II machine at the UMASS Medical Center. The space group is C222, with two molecules in the asymmetric unit. The unit cell dimensions are a= 117.048
, b= 132.649
, c= 134.989
. However, the Rmerge of the diffraction data is 15%. Therefore, we are applying for the synchrotron time to collect a set of high resolution native data at CHESS. We intend to solve the structure with the molecular replacement method, by using the crystal structure of PTP1B as the search model. The sequence identity between PTP1B and PTP1C is 35%. If necessary, we will screen the heavy atom derivatives using the RAXIS machine at the UMASS Medical Center.