Quantum mechanical models of the resting state of the vanadium-dependent haloperoxidase.
Quantum mechanical models of the resting state of the vanadium-dependent haloperoxidase.
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DOI：
10.1021/ic0353256
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发表时间：
2004-04
影响因子：
4.6
通讯作者：
Giuseppe Zampella;Joslyn Yudenfreund Kravitz;C. E. Webster;P. Fantucci;M. Hall;H. Carlson;V. Pecoraro-
中科院分区：
文献类型：
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作者：
Giuseppe Zampella;Joslyn Yudenfreund Kravitz;C. E. Webster;P. Fantucci;M. Hall;H. Carlson;V. Pecoraro-
利用密度泛函理论研究了钒卤代过氧化物酶活性中心的静息态与环境和质子化状态的关系。通过研究不同大小和复杂性的模型所获得的结果突出了环境和质子化状态对金属辅因子的结构和稳定性的影响。研究表明，在三角双锥活性位点中，其中一个轴向位置被一个关键的组氨酸占据，反式位置不能包含末端氧代基团。此外，高度负电荷的钒酸盐单元是不稳定的。质子化的至少一个赤道氧代配体似乎是必要的，以稳定的金属辅因子。该研究还表明，在蛋白质内静止时，钒酸盐单元最有可能是具有轴向氢氧化物和含有两个oxos和一个氢氧化物的赤道平面的阴离子。对于钒酸盐单元的中性质子化状态，发现了两个最小值。第一种结构的特征是在赤道平面上具有两个氧代和一个羟基团的轴向水。第二种结构包含轴向羟基和由一个氧代和两个羟基氧原子组成的赤道平面。这两种物质在能量上没有显着差异，表明在催化循环中，任何一种形式都可能是重要的。这些数据支持轴向结合的氢氧化物的初始晶体学分配，但轴向水也是一种可能性。这项研究还表明，钒酸根离子的质子化状态是最有可能大于以前提出的。
Density functional theory has been used to investigate structural and electronic properties of complexes related to the resting form of the active site of vanadium haloperoxidase as a function of environment and protonation state. Results obtained by studying models of varying size and complexity highlight the influence of environment and protonation state on the structure and stability of the metal cofactor. The study shows that, in the trigonal bipyramidal active site, where one axial position is occupied by a key histidine, the trans position cannot contain a terminal oxo group. Further, a highly negatively charged vanadate unit is not stable. Protonation of at least one equatorial oxo ligand appears necessary to stabilize the metal cofactor. The study also indicates that, while at rest within the protein, the vanadate unit is most likely an anion with an axial hydroxide and an equatorial plane containing two oxos and a hydroxide. For the neutral, protonated state of the vanadate unit, there were two minima found. The first structure is characterized by an axial water with two oxo and one hydroxo group in the equatorial plane. The second structure contains an axial hydroxo group and an equatorial plane composed of one oxo and two hydroxo oxygen atoms. These two species are not significantly different in energy, indicating that either form may be important during the catalytic cycle. These data support the initial crystallographic assignment of an axially bound hydroxide, but an axial water is also a possibility. This study also shows that the protonation state of the vanadate ion is most likely greater than previously proposed.