PROLYL ISOMERASE PIN1S INTERACTION W/ MITOTICALLY PHOSPHORYLATED SUBSTRATES

结合1.35E晶体结构的功能研究 Pin1立即显示对磷酸化的丝氨酸/苏氨酸的偏好 N-末端用于在其目标选择中添加脯氨酸。在努力实现 将这些交互作用可视化并阐明PIN1的机制 介导性多肽键异构化我们已经开始共结晶 Pin1-多肽复合体以及Pin1晶体与 磷酸-丝氨酸-Pro二肽。泛素连接酶(E3)决定 泛素介导的蛋白质降解的选择性。结构性 对这些泛素连接酶的研究对于阐明它们的 反应机理及其最重要的靶向模式 选择。我们已经生长了类似Nedd4的泛素连接酶的晶体 空间群P1中的Hect结构域。

Functional studies combined with the 1.35 E crystal structure of Pin1 show a preference for a phosphorylated Ser/Thr immediately N-terminal to proline in its target selection. In efforts to visualize these interactions and clarify the mechanism of Pin1 mediated peptide bond isomerization we have begun co-crystallization of Pin1-peptide complexes as well as soaks of Pin1 crystals with phospho-Ser-Pro dipeptides. Ubiquitin ligases (E3) determine the selectivity of ubiquitin-mediated protein degradation. Structural studies of these ubiquitin ligases are crucial in elucidating their reaction mechanisms and most importantly their mode of target selection. We have grown crystals of the Nedd4-like ubiquitin ligase hect-domain in space group P1.