Jaffrey S R, Snyder S H
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Science. 1996 Nov 1;274(5288):774-7. doi: 10.1126/science.274.5288.774.
The neurotransmitter functions of nitric oxide are dependent on dynamic regulation of its biosynthetic enzyme, neuronal nitric oxide synthase (nNOS). By means of a yeast two-hybrid screen, a 10-kilodalton protein was identified that physically interacts with and inhibits the activity of nNOS. This inhibitor, designated PIN, appears to be one of the most conserved proteins in nature, showing 92 percent amino acid identity with the nematode and rat homologs. Binding of PIN destabilizes the nNOS dimer, a conformation necessary for activity. These results suggest that PIN may regulate numerous biological processes through its effects on nitric oxide synthase activity.
一氧化氮的神经递质功能依赖于其生物合成酶——神经元型一氧化氮合酶（nNOS）的动态调节。通过酵母双杂交筛选，鉴定出一种10千道尔顿的蛋白质，它与nNOS发生物理相互作用并抑制其活性。这种抑制剂被命名为PIN，它似乎是自然界中最保守的蛋白质之一，与线虫和大鼠的同源物具有92%的氨基酸同一性。PIN的结合会使nNOS二聚体不稳定，而二聚体是其发挥活性所必需的构象。这些结果表明，PIN可能通过影响一氧化氮合酶的活性来调节众多生物学过程。
