Specificity and Function in Neural Endopeptidases

神经内肽酶的特异性和功能。小肽分子有助于在神经系统中传递信息，调节神经活动，并改变神经系统外其他组织的功能。这项研究的目的是了解控制这些神经肽水平的酶是如何起作用的——它们是如何识别目标分子的，它们是如何将它们切割成更小的片段的，以及它们是如何避免不恰当地攻击存在的许多其他分子的。我们将结合两种方法来解决这个问题。首先，我们将使用x射线技术提供一种称为内肽酶24.16的这种酶的详细的三维图像。从这个内肽酶24.16的结构，我们将能够可视化酶是如何结合和切割其目标肽的。其次，我们将使用生化方法来更好地定义内肽酶24.16的良好靶点的特征。最终，从这些研究中获得的信息将增加我们为特定任务设计蛋白质的能力。

Lay SummarySpecificity and Function in Neural Endopeptidases.Small peptide molecules help to carry information in the nervous system, regulate neural activity, and alter the function of other tissues outside the nervous system. The goal of this study is to understand how enzymes that control the levels of these neuropeptides function -how they recognize their target molecules, how they act to cleave them into smaller pieces, and how they avoid attacking inappropriately the many other molecules present. We will combine two approaches to the problem. First, we will use x-ray techniques to provide a detailed, three-dimensional picture of one such enzyme known as endopeptidase 24.16. From this structure of endopeptidase 24.16, we will be able to visualize how the enzyme might bind to and cleave its target peptides. Second, we will use biochemical approaches to better define the characteristics of a good target for endopeptidase 24.16. Ultimately, the information obtained from these studies will add to our ability to engineer proteins for specific tasks.