Quantitative 13C and 2H NMR relaxation studies of the 723-residue enzyme malate synthase g reveal a dynamic binding lnterface
Quantitative 13C and 2H NMR relaxation studies of the 723-residue enzyme malate synthase g reveal a dynamic binding lnterface
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DOI：
10.1021/bi0519809
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发表时间：
2005-12-13
期刊：
影响因子：
2.9
通讯作者：
Kay, LE
中科院分区：
文献类型：
--
作者：
Tugarinov, V;Kay, LE
对分子识别的详细理解不仅取决于自由态和束缚态的高分辨率静态结构，还取决于这些结构如何随时间变化的信息，即分子动力学。在这里，我们提出了一个氘（H-2）和碳（C-13）NMR弛豫研究的甲基侧链动力学在82 kDa的酶苹果酸合酶G（MSG），这是一个有前途的目标，为新的抗生素制剂的发展。结果表明，H-2-和C-13-衍生的动态措施之间的良好协议，获得相关系数超过0.95。MSG与其底物形成的结合界面在酶的无配体状态下是高度动态的，在结合底物时会发生硬化。这项研究建立了详细的，定量的信息甲基侧链动力学可以通过NMR获得的蛋白质分子量的顺序为100 kDa，并开辟了运动的研究在大量的重要系统的可能性。
A detailed understanding of molecular recognition is predicated not only on high-resolution static structures of the free and bound states but also on information about how these structures change with time, that is, molecular dynamics. Here we present a deuterium (H-2) and carbon (C-13) NMR relaxation study of methyl side chain dynamics in the 82 kDa enzyme malate synthase G (MSG) that is a promising target for the development of new antibiotic agents. It is shown that excellent agreement between H-2- and C-13-derived measures of dynamics is obtained, with correlation coefficients exceeding 0.95. The binding interface formed by MSG and its substrates is found to be highly dynamic in the ligand-free state of the enzyme with rigidification upon binding substrate. This study establishes that detailed, quantitative information about methyl side chain dynamics can be obtained by NMR on proteins with molecular masses on the order of 100 kDa and opens up the possibilities for studies of motion in a large number of important systems.