Mattevi A, Bolognesi M, Valentini G
Department of Genetics & Microbiology, University of Pavia, Italy.
FEBS Lett. 1996 Jun 24;389(1):15-9. doi: 10.1016/0014-5793(96)00462-0.
Crystallographic and mutagenesis studies have unravelled the general features of the allosteric transition mechanism in pyruvate kinase. The enzyme displays a dramatic conformational change in going from the T- to the R-state. All three domains forming each subunit of the tetrameric enzyme undergo simultaneous and concerted rotations, in such a way that all subunit and domain interfaces are modified. This mechanism is unprecedented since in all tetrameric allosteric enzymes, characterised at atomic resolution, at least one of the domain or subunit interfaces remains unchanged on the T- to R-state transition. The molecular mechanism of allosteric regulation here proposed provides a rationale for the effect of single site mutations observed in the human erythrocyte pyruvate kinase associated with a congenital anaemia.
晶体学和诱变研究揭示了丙酮酸激酶变构转换机制的一般特征。该酶从T态转变为R态时会发生显著的构象变化。构成四聚体酶每个亚基的所有三个结构域会同时协同旋转，从而使所有亚基和结构域界面都发生改变。这种机制是前所未有的，因为在所有以原子分辨率表征的四聚体变构酶中，在从T态到R态的转变过程中，至少有一个结构域或亚基界面保持不变。这里提出的变构调节分子机制为在与先天性贫血相关的人类红细胞丙酮酸激酶中观察到的单一位点突变的影响提供了理论依据。
