Ro 90-7501 inhibits PP5 through a novel, TPR-dependent mechanism
Ro 90-7501 inhibits PP5 through a novel, TPR-dependent mechanism
复制标题
DOI：
10.1016/j.bbrc.2016.11.043
复制
发表时间：
2017-01-08
影响因子：
3.1
通讯作者：
Hahn, Ji-Sook
中科院分区：
文献类型：
--
作者：
Hong, Tae-Joon;Park, Kwanghyun;Hahn, Ji-Sook
蛋白磷酸酶5（PP 5）是属于PPP家族磷酸酶的丝氨酸/苏氨酸磷酸酶。PP 5和PPP家族的其他磷酸酶共享显著相似的催化结构域结构。由于这种结构上的相似性，天然竞争性抑制剂如冈田酸和藜芦苷对PPP家族磷酸酶表现出广泛的特异性。在这项研究中，我们报告了三个PP 5抑制剂，Ro 90-7501，aurothioglucose，和N-油酰多巴胺，沿着一个新的抑制机制Ro 90-7501的鉴定。与其他结合磷酸酶结构域的抑制剂不同，Ro 90-7501以TPR依赖性方式抑制PP 5。Ro 90-7501对PP 5的这种TPR依赖性抑制是一种独特的、新颖的抑制机制，可能为PP 5的调控机制研究和药物开发提供有用的工具。(C)2016 Elsevier Inc. All rights reserved.
Protein phosphatase 5 (PP5) is a serine/threonine phosphatase that belongs to the PPP family phosphatases. PP5 and the other phosphatases of the PPP family share significantly similar catalytic domain structure. Due to this structural similarity, natural competitive inhibitors such as okadaic acid and cantharidin exhibit broad specificity over the PPP family phosphatases. In this study, we report the identification of three PP5 inhibitors, Ro 90-7501, aurothioglucose, and N-oleoyldopamine, along with a novel inhibitory mechanism of Ro 90-7501. Unlike other inhibitors binding to the phosphatase domain, Ro 90-7501 inhibited PP5 in a TPR-dependent manner. This TPR-dependent PP5 inhibition shown by Ro 90-7501 is a unique and novel inhibitory mechanism, which might be a useful tool for studies of PP5 on both regulatory mechanism and drug discovery. (C) 2016 Elsevier Inc. All rights reserved.