Faculty of Chemistry, University of Wrocław, Joliot-Curie 14, 50-383, Wrocław, Poland.
Mol Divers. 2011 Feb;15(1):215-26. doi: 10.1007/s11030-010-9256-3. Epub 2010 May 20.
Mercury(II) has a strong affinity for the thiol groups in proteins often resulting in the disruption of their biological functions. In this study we present classical and first-principles, DFT-based molecular dynamics (MD) simulations of a complex of Hg(II) and proteinase K, a well-known serine protease with a very broad and diverse enzymatic activity. It contains a catalytic triad formed by Asp39, His69, and Ser224, which is responsible for its biological activity. It was found previously by X-ray diffraction experiments that the presence of Hg(II) inhibits the enzymatic action of proteinase K by affecting the stereochemistry of the triad. Our simulations predict that (i) the overall structure as well as the protein backbone dynamics are only slightly affected by the mercury cation, (ii) depending on the occupied mercury site, the hydrogen bonds of the catalytic triad are either severely disrupted (both bonds for mercury at site 1, and the His69-Ser224 contact for mercury at site 2) or slightly strengthened (the Asp39-His69 bond when mercury is at site 2), (iii) the network of hydrogen bonds of the catalytic triad is not static but undergoes constant fluctuations, which are significantly modified by the presence of the Hg(II) cation, influencing in turn the triad's ability to carry out the enzymatic function--these facts explain the experimental findings on the inhibition of proteinase K by Hg(II).
汞（II）与蛋白质中的巯基具有很强的亲和力，通常会破坏其生物功能。在这项研究中，我们对汞（II）与蛋白酶 K 的复合物进行了经典和基于第一性原理的、基于密度泛函理论的分子动力学（MD）模拟，蛋白酶 K 是一种具有非常广泛和多样的酶活性的丝氨酸蛋白酶。它包含一个由 Asp39、His69 和 Ser224 组成的催化三联体，负责其生物活性。先前的 X 射线衍射实验发现，汞（II）的存在通过影响三联体的立体化学来抑制蛋白酶 K 的酶促作用。我们的模拟预测：（i）汞阳离子仅对整体结构和蛋白质骨架动力学产生轻微影响，（ii）根据占据的汞位，催化三联体的氢键要么严重破坏（汞位于位 1 时的两个键，以及汞位于位 2 时 His69-Ser224 接触），要么稍微增强（汞位于位 2 时的 Asp39-His69 键），（iii）催化三联体的氢键网络不是静态的，而是不断波动的，汞（II）阳离子的存在极大地改变了氢键网络，从而影响了三联体执行酶功能的能力——这些事实解释了实验发现的汞（II）对蛋白酶 K 的抑制作用。
