Allosteric Mechanism of Pyruvate Kinase from Leishmania mexicana Uses a Rock and Lock Model
Allosteric Mechanism of Pyruvate Kinase from Leishmania mexicana Uses a Rock and Lock Model
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DOI：
10.1074/jbc.m109.079905
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发表时间：
2010-04-23
影响因子：
4.8
通讯作者：
Walkinshaw, Malcolm D.
中科院分区：
文献类型：
--
作者：
Morgan, Hugh P.;McNae, Iain W.;Walkinshaw, Malcolm D.
变构调节为参与许多细胞过程的酶提供了一种速率管理系统。配体控制的调控很容易识别，但潜在的分子机制仍然难以捉摸。我们已经获得了墨西哥利什曼原虫四聚体酶丙酮酸激酶在所有可能的连接状态下的第一个完整的变构结构系列。在非活动的T-态和活动的R-态之间的转变伴随着四个亚单位中的A和C域核的简单对称的6度刚体摆动运动。然而，以这种方式形成R态只是机制的一部分；跨越C-C界面形成的八个基本盐桥锁提供了四聚体的刚性，结合速度增加了7倍。本文的结果说明了构象变化和效应器结合如何与柔韧性的丧失和热稳定性的增加相关，为变构控制提供了一个一般的机制。
Allosteric regulation provides a rate management system for enzymes involved in many cellular processes. Ligand-controlled regulation is easily recognizable, but the underlying molecular mechanisms have remained elusive. We have obtained the first complete series of allosteric structures, in all possible ligated states, for the tetrameric enzyme, pyruvate kinase, from Leishmania mexicana. The transition between inactive T-state and active R-state is accompanied by a simple symmetrical 6 degrees rigid body rocking motion of the A- and C-domain cores in each of the four subunits. However, formation of the R-state in this way is only part of the mechanism; eight essential salt bridge locks that form across the C-C interface provide tetramer rigidity with a coupled 7-fold increase in rate. The results presented here illustrate how conformational changes coupled with effector binding correlate with loss of flexibility and increase in thermal stability providing a general mechanism for allosteric control.