The planar conformation of a strained proline ring: A QM/MM study
The planar conformation of a strained proline ring: A QM/MM study
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DOI：
10.1002/prot.21006
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发表时间：
2006-08-15
影响因子：
2.9
通讯作者：
Juffer, Andre H.
中科院分区：
文献类型：
--
作者：
Donnini, Serena;Groenhof, Gerrit;Juffer, Andre H.
QM和QM/MM能量计算已经进行了配体磷酸丙糖异构酶（TIM），具有一个活性位点脯氨酸（Pro 168）在一个平面构象的原子分辨率结构。这脯氨酸的平面性的起源已被确定。脯氨酸环的原子与脯氨酸一侧的酪氨酸环（Tyr 166）之间的空间相互作用防止该环采用向上褶皱（chi（1）约为-30度，而附近丙氨酸（Ala 171）的侧链禁止向下褶皱（chi（1）约为+30度）。为了获得与实验观察到的平面状态一致的脯氨酸构象，需要足够大小的量子系统，并且至少应该包括Tyr 166、Ala 171和Glu 129的附近侧链以提供足够的稳定性。有人认为，目前的力场结构优化不正确描述应变蛋白质片段。脯氨酸是在配体结合时关闭的催化环的一部分。比较不同TIM X射线结构中的脯氨酸构象，表明在TIM的闭合构象中脯氨酸是平面或接近平面的，而在打开构象中脯氨酸是向下起皱的。这表明平面性可能在TIM的整个催化循环中起作用，推测其充当在环打开时变得可用的能量的储存器。
QM and QM/MM energy calculations have been carried out on an atomic resolution structure of liganded triosephosphate isomerase (TIM) that has an active site proline (Pro168) in a planar conformation. The origin of the planarity of this proline has been identified. Steric interactions between the atoms of the proline ring and a tyrosine ring (Tyr166) on one side of the proline prevent the ring from adopting the up pucker (chi(1) is approximately -30 degrees while the side chain of a nearby alanine (Ala171) forbids the down pucker (chi(1) is approximately +30 degrees). To obtain a proline conformation that is in agreement with the experimentally observed planar state, a quantum system of sufficient size is required and should at least include the nearby side chains of Tyr166, Ala171, and Glu129 to provide enough stabilization. It is argued that the current force fields for structure optimization do not describe strained protein fragments correctly. The proline is part of a catalytic loop that closes upon ligand binding. Comparison of the proline conformation in different TIM X-ray structures, indicates that in the closed conformation of TIM the proline is planar or nearly planar, while in the open conformation it is down puckered. This suggests that the planarity possibly plays a role in the overall catalytic cycle of TIM, presumable acting as a reservoir of energy that becomes available upon loop opening.