Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark.
J Med Chem. 2013 May 9;56(9):3609-19. doi: 10.1021/jm4001083. Epub 2013 Apr 30.
A crystal structure suggests four water molecules are present in the binding cavity of thapsigargin in sarco/endoplasmic reticulum calcium ATPase (SERCA). Computational chemistry indicates that three of these water molecules mediate an extensive hydrogen-bonding network between thapsigargin and the backbone of SERCA. The orientation of the thapsigargin molecule in SERCA is crucially dependent on these interactions. The hypothesis has been verified by measuring the affinity of newly synthesized model compounds, which are prevented from participating in such water-mediated interactions as hydrogen-bond donors.
晶体结构表明，在肌浆/内质网钙 ATP 酶（SERCA）中，他泊糖苷结合腔内存在四个水分子。计算化学表明，这三个水分子介导了他泊糖苷和 SERCA 骨架之间广泛的氢键网络。他泊糖苷分子在 SERCA 中的取向极大地依赖于这些相互作用。这一假说已通过测量新合成的模型化合物的亲和力得到验证，这些化合物被阻止作为氢键供体参与这种水介导的相互作用。
