Chemical Library Validation Team, Chemical Biology Core Facility, Chemical Biology Department, RIKEN Advanced Science Institute, Wako, Saitama, Japan.
Nat Chem Biol. 2010 Sep;6(9):667-73. doi: 10.1038/nchembio.423. Epub 2010 Aug 15.
The discovery of small molecules that bind to a specific target and disrupt the function of proteins is an important step in chemical biology, especially for poorly characterized proteins. Human pirin is a nuclear protein of unknown function that is widely expressed in punctate subnuclear structures in human tissues. Here, we report the discovery of a small molecule that binds to pirin. We determined how the small molecule bound to pirin by solving the cocrystal structure. Either knockdown of pirin or treatment with the small molecule inhibited melanoma cell migration. Thus, inhibition of pirin by the small molecule has led to a greater understanding of the function of pirin and represents a new method of studying pirin-mediated signaling pathways.
小分子与特定靶标结合并破坏蛋白质功能的发现是化学生物学的重要步骤，特别是对于功能尚未明确的蛋白质而言。人源吡啉蛋白（pirin）是一种核蛋白，其功能未知，但在人体组织中呈点状的亚核结构广泛表达。在此，我们报道了小分子与吡啉蛋白结合的发现。我们通过解析共晶结构确定了小分子与吡啉蛋白的结合方式。敲低吡啉蛋白或用小分子处理均能抑制黑色素瘤细胞迁移。因此，小分子对吡啉蛋白的抑制作用增进了对其功能的理解，也为研究吡啉蛋白介导的信号通路提供了新方法。
