STRUCTURE DETERMINATION OF TAHO

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 端锚聚合酶1和端锚聚合酶2（TaHO）是具有聚（ADP-核糖）聚合酶（PARP）活性的端粒相关蛋白，其正调节端粒长度并且可能有助于维持端粒结构。端锚聚合酶使用NAD+作为底物来催化ADP-核糖聚合物在蛋白质（包括其自身）上的形成。 端锚聚合酶介导的端粒结合蛋白TRF 1的聚（ADP-核糖基）化导致其从端粒释放并诱导与细胞增殖相关的端粒延长。 端锚聚合酶抑制预期会破坏端粒结构，从而引起染色体末端融合，导致细胞死亡。 本提案的目的是确定端锚聚合酶的人类同源物的聚ADP核糖聚合酶（PARP）结构域的结构。 已经收集了3.0埃的天然数据集，并且已经针对结构解决方案广泛测试了分子置换。 需要重原子定相信息来确定这种蛋白质的结构。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Tankyrases 1 and 2 (TaHO) are telomere-associated proteins with poly(ADP-ribose) polymerase (PARP) activity that positively regulate telomere length and may contribute to maintenance of telomere structure. Tankyrases use NAD+ as a substrate to catalyze formation of ADP-ribose polymers onto proteins including themselves. Tankyrase mediated poly(ADP- ribosyl)ation of the telomere binding protein TRF1 results in its release from telomeres and induces telomere elongation associated with cell proliferation. Tankyrase inhibition is expected to disrupt telomere structure, thereby causing chromosomal end fusions that result in cell death. The objective of this proposal is to determine the structure of the poly- ADP ribose polymerase (PARP) domain of a human homologue of tankyrase. A native data set has been collected to 3.0 Angstrom and molecular replacement has been extensively tested for structure solution. Heavy atom phasing information will be needed to determine the structure of this protein.