Schweins T, Geyer M, Scheffzek K, Warshel A, Kalbitzer H R, Wittinghofer A
Max-Planck-Institut für molekulare Physiologie, Abteilung Strukturelle Biologie, Dortmund, Germany.
Nat Struct Biol. 1995 Jan;2(1):36-44. doi: 10.1038/nsb0195-36.
Despite many advances in understanding the structure and function of GTP-binding proteins the mechanism by which these molecules switch from the GTP-bound on-state to the GDP-bound off-state is still poorly understood. Theoretical studies suggest that the activation of the nucleophilic water which hydrolyzes GTP needs a general base. Such a base could not be located in any of the many GTP-binding proteins. Here we present a unique type of linear free energy relationships that not only supports a mechanism for p21ras in which the substrate GTP itself acts as the catalytic base driving the GTPase reaction but can also help to explain why certain mutants of p21ras are oncogenic and others are not.
尽管在理解GTP结合蛋白的结构和功能方面取得了许多进展，但这些分子从结合GTP的开启状态转变为结合GDP的关闭状态的机制仍知之甚少。理论研究表明，水解GTP的亲核水的活化需要一个通用碱。在众多GTP结合蛋白中均未找到这样的碱。在此，我们提出了一种独特类型的线性自由能关系，它不仅支持p21ras的一种机制，即底物GTP自身充当驱动GTP酶反应的催化碱，而且还有助于解释为什么p21ras的某些突变体具有致癌性而其他突变体则不然。
