CO-CRYSTAL STRUCTURES OF LIPID KINASES WITH SMALL MOLECULE INHIBITORS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们的目标是在我们的基于结构的支架发现平台上衍生出一系列抑制剂的复合体中，确定蛋白质和脂激酶治疗靶点的高分辨率共晶结构。我们的研究在很大程度上依赖于像SSRL这样的机构的X射线衍射资源，以阐明小分子抑制剂与激酶靶标的复合体的分子相互作用。这些靶点在不同的病理生理过程中非常重要，例如肿瘤的发生和转移。用小分子抑制剂靶向这些酶使其有可能治疗包括癌症在内的人类疾病。对于某些激酶靶，我们无法获得大于50M的共晶，这往往导致用常规X射线源进行低分辨率的衍射。因此，获得微聚焦光束线有可能成为基于结构的激酶治疗研究的一种有价值的新资源。

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. Our goal is to determine high resolution co-crystal structures of protein and lipid kinase therapeutic targets in complex with a series of inhibitors derived from our structure-based scaffold discovery platform. Our research relies heavily on the x-ray diffraction resources at institutions like SSRL in order to elucidate the molecular interactions of small molecule inhibitors in complex with kinase targets. These targets are important in diverse pathophysiological processes, such as tumorigenesis and metastasis. Targeting these enzymes with small molecule inhibitors enables the potential to treat human disease including cancers. For some kinase targets, we are not able to obtain co-crystals larger than 50 ?m which often leads to low-resolution diffraction with conventional x-ray sources. Therefore, access to a micro-focus beam line has the potential to be a valuable new resource for structure-based kinase therapy research.