NORMAL MODE ANALYSIS OF HUMAN LYSOZYME - STUDY OF THE RELATIVE MOTION OF THE 2 DOMAINS AND CHARACTERIZATION OF THE HARMONIC MOTION
NORMAL MODE ANALYSIS OF HUMAN LYSOZYME - STUDY OF THE RELATIVE MOTION OF THE 2 DOMAINS AND CHARACTERIZATION OF THE HARMONIC MOTION
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DOI：
10.1002/prot.340080308
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发表时间：
1990-01-01
影响因子：
2.9
通讯作者：
GO, N
中科院分区：
文献类型：
--
作者：
GIBRAT, JF;GO, N
在室温下对人溶菌酶进行了简正模式分析。人溶菌酶是一种由活性部位裂隙隔开的两个结构域组成的酶，其运动被认为与生物功能有关。这项运动被描述为铰链弯曲运动。McCammon等人。已经确定了铰链弯曲运动的特征，但他们假设了铰链轴线的先验知识。在这项工作中，我们提出了一种摆脱这一假设的方法，并确定了铰链轴和均方根(RMS)旋转角，它们与通过简正波分析得到的两个区域中非氢原子之间的所有距离的变化规律最吻合。我们发现的铰链轴与先前确定的显著不同，大致穿过Cα55和Cα76，即它位于第二结构域的β-折叠的底部。旋转角度的均方根值也是前一个的两倍：3.37度。结果表明，这种铰链弯曲运动对人体溶菌酶的动力学有很好的近似，最低频率的简正模对这种铰链弯曲运动有主要的贡献。对裂隙内残基的可接近表面积的研究表明，该运动并不会导致更好地暴露于这些残基的溶剂中。利用原子堆积的拓扑概念，对热激发态(在势能面的谐和假设下)进行了表征。在这一假设下，热涨落只会导致原子堆积的拓扑结构发生很小的变化，从而导致蛋白质的近乎弹性变形。
A normal mode analysis of human lysozyme has been carried out at room temperature. Human lysozyme is an enzyme constituted of two domains separated by an active site cleft, the motion of which is thought to be relevant for biological function. This motion has been described as a hinge bending motion. McCammon et al. have determined the characteristics of the hinge bending motion but they assumed a prior knowledge of the hinge axis. In this work we propose a method which is free from this assumption and determines the hinge axis and root mean square (rms) rotation angle which give the best agreement with the pattern of changes in all the distances between nonhydrogen atoms in the two domains, obtained by the normal mode analysis. The hinge axis we found is notably different from the one previously determined and goes, roughly, through the C.alpha.55 and C.alpha.76, i.e., it is located at the base of the .beta.-sheet of the second domain. The rms value for the rotation angle is also twice as large as the previous one: 3.37.degree.. it is shown that this hinge bending motion provides a fairly good approximation of the dynamics of human lysozyme and that the normal mode with the lowest frequency has a dominating contribution to this hinge bending motion. A study of the accessible surface area of the residues within the cleft reveals that the motion does not result in a better exposure to the solvent of these residues. A characterization of the thermally excited state (under the hypothesis of the harmonicity of the potential energy surface) has been done using the concept of topology of atom packing. Under this hypothesis the thermal fluctuations result only in a small change of the topology of atom packing, leading therefore to nearly elastic deformations of the protein.