Molecular dynamics simulation of bovine prothrombin fragment 1 in the presence of calcium ions.
Molecular dynamics simulation of bovine prothrombin fragment 1 in the presence of calcium ions.
复制标题
钙离子存在下牛凝血酶原片段 1 的分子动力学模拟。
DOI：
10.1021/bi00152a021
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发表时间：
1992
期刊：
影响因子：
2.9
通讯作者：
Pedersen,L
中科院分区：
文献类型：
--
作者：
Hamaguchi,N;Charifson,P;Darden,T;Xiao,L;Padmanabhan,K;Tulinsky,A;Hiskey,R;Pedersen,L
1992年7月2日收到的修订版摘要：用分子动力学模拟凝血酶原钙片段1的早期溶剂化诱导的结构重组。初始坐标是2.2-nm分辨率晶体结构的坐标[Soriano-Garcia，M.，Padmanabhan，K.，de Vos，AM，& Tulinsky，A.（1992）Biochemistry 31，2554-2556]。分子动力学代码AMBER，适当修改以包括长程（< 22.0 μ m）离子力，被采用。溶液结构似乎在100 ps内平衡。虽然在各种结构域中观察到微小的变化，但早期溶液结构基本上保持了包裹七个钙离子的九个羧基谷氨酸（Gla）残基的复杂网络。然而，Gla结构域相对于Kringle结构域移动。这种运动主要是由于Ser 34-Leu 35的运动，它似乎是结构域之间的柔性铰链。阿莱的N-末端是在一个紧密结合的复杂的三个Gla残基，保持稳定的溶液结构时，远程静电截止和近平面排列的7个钙离子只有轻微的扭曲。通过钙离子诱导的内源荧光猝灭、钙离子对N-末端氨基乙酰化的保护、N-末端三硝基苯基衍生物的化学修饰以及Kringle结构域中钙结合位点的可能性等实验，讨论了模拟结构。凝血酶原是参与凝血级联反应的几种维生素K依赖性蛋白之一，通过膜表面的凝血酶原酶复合物转化为凝血酶（Suttie &杰克逊，1977）。凝血酶随后催化纤维蛋白原转化为纤维蛋白，形成基本的纤维蛋白凝块。凝血酶还在增强、减弱和调节其他止血过程中发挥重要的生理作用（Mann，1987）。牛凝血酶原的片段1是蛋白质的1-156 N端肽（图1），可与膜结合。N-末端区域的前33个残基中的10个谷氨酸残基通常被维生素K依赖性羧化酶后修饰为Gla 1（Suttie，1988;
Revised Manuscript Received July 2, 1992 abstract: Early solvation-induced structural reorganization of calcium prothrombin fragment 1 is simulated with molecular dynamics. Initial coordinates are those of the 2.2-Á resolution crystal structure [Soriano-Garcia, M., Padmanabhan, K., de Vos, AM, & Tulinsky, A.(1992) Biochemistry 31, 2554-2556]. The molecular dynamics code AMBER, appropriately modified to include long-range (< 22.0 Á) ionic forces, was employed. The solution structure appears to equilibrate within 100 ps. Although minor changes are seen in various structural domains, the early solution structure basically maintains an intricate network of nine-carboxyglutamic acid (Gla) residues encapsulating seven calcium ions. However, the Gla domain moves with respect to the kringle domain. This motion is mainly due to the movement of Ser34-Leu35 that appears to be a flexible hingebetween the domains. The N-terminus of Alai is in a tightly bound complex with three Gla residues that remains stable in the solution structure when the long-range electrostatic cutoff is employed and the near planar alignment of the seven calcium ions is only slightly distorted. The simulation structure is discussed in terms of experiments that studied calcium ion-induced quenching of the intrinsic fluorescence, protection of the N-terminal amino group from acetylation by calcium ions, chemical modification of the N-terminus to a trinitrophenyl derivative, and the possibility of a calciumbinding site (s) in the kringle domain.Prothrombin, one of several vitamin-K dependent proteins involved in the blood coagulation cascade, is converted to thrombin by the prothrombinase complex on the surface of membranes (Suttie & Jackson, 1977). Thrombin subsequently catalyzes the conversion of fibrinogen to fibrin that forms the essential fibrin clot. Thrombin also plays an important physiological role in the enhancement, attenuation, and regulation of other haemostatic processes (Mann, 1987). Fragment 1 of bovine prothrombin is the 1-156 N-terminal peptide of the protein (Figure 1) that can bind to membrane. Ten glutamic acid residues within the first 33 residues of the N-terminus region are normally posttranslationally modified by a vitamin-K dependent carboxylase to Gla1 (Suttie, 1988;