Tarragó Teresa, Martín-Benito Jaime, Sabidó Eduard, Claasen Birgit, Madurga Sergio, Gairí Margarida, Valpuesta José M, Giralt Ernest
Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac, 10, E-08028, Barcelona, Spain.
FEBS Lett. 2009 Oct 20;583(20):3344-8. doi: 10.1016/j.febslet.2009.09.036. Epub 2009 Sep 25.
Prolyl oligopeptidase (POP) has gained importance as a target for the treatment of neuropsychiatric diseases and cognitive disturbances. Therefore, a variety of strategies are currently used to identify POP inhibitors. Here we performed electron microscopy (EM) studies of human POP. Our data reveal for the first time the presence of a new side opening in POP that was not observed in any of the crystallographic structures described to date. Finally, molecular dynamics, the relevant normal modes that contribute to the fluctuation of the catalytic triad residues and the algorithm CAVERN also support the existence of a new large side opening on POP.
脯氨酰寡肽酶（POP）作为神经精神疾病和认知障碍治疗的靶点已变得越发重要。因此，目前人们采用了多种策略来鉴定POP抑制剂。在此，我们对人源POP进行了电子显微镜（EM）研究。我们的数据首次揭示了POP中存在一个新的侧向开口，这在迄今为止所描述的任何晶体结构中均未观察到。最后，分子动力学、有助于催化三联体残基波动的相关正常模式以及CAVERN算法也支持了POP上存在一个新的大侧向开口。
