Structural Changes of the Trinuclear Copper Center in Bilirubin Oxidase upon Reduction
Structural Changes of the Trinuclear Copper Center in Bilirubin Oxidase upon Reduction
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DOI：
10.3390/molecules24010076
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发表时间：
2019-01-01
期刊：
影响因子：
4.6
通讯作者：
Misaizu, Fuminori
中科院分区：
文献类型：
--
作者：
Tokiwa, Takaki;Shoji, Mitsuo;Misaizu, Fuminori
采用量子力学/分子力学（QM/MM）方法研究了胆红素氧化酶（BOD）中铜（Cu）中心在四电子还原过程中的几何和电子结构变化.对于QM区域，采用非限制密度泛函理论（UDFT）方法对开壳层体系进行计算。我们发现了天然中间体（NI，中间体II）和静息氧化（RO）状态的新候选者，即，NIH+和RO 0。作为四电子还原的结果，计算了三核Cu中心（TNC）和I型Cu（T1 Cu）周围非常小的结构变化的Cu-Cu原子距离的延长。QM/MM优化结构与最近的高分辨率X射线结构吻合良好。由于TNC在还原时的结构变化被揭示为TNC的三个Cu原子所跨越的三角形的大小的变化，我们引入了一个新的指数（l）来表征特定的结构变化。不仅野生型，而且M467 Q，其突变的氨基酸残基配位T1 Cu，精确地分析了它们的分子轨道水平，并优化T1 Cu的氧化还原电位从理论上重新确认。
Geometric and electronic structure changes in the copper (Cu) centers in bilirubin oxidase (BOD) upon a four-electron reduction were investigated by quantum mechanics/molecular mechanics (QM/MM) calculations. For the QM region, the unrestricted density functional theory (UDFT) method was adopted for the open-shell system. We found new candidates of the native intermediate (NI, intermediate II) and the resting oxidized (RO) states, i.e., NIH+ and RO0. Elongations of the Cu-Cu atomic distances for the trinuclear Cu center (TNC) and very small structural changes around the type I Cu (T1Cu) were calculated as the results of a four-electron reduction. The QM/MM optimized structures are in good agreement with recent high-resolution X-ray structures. As the structural change in the TNC upon reduction was revealed to be the change in the size of the triangle spanned by the three Cu atoms of TNC, we introduced a new index (l) to characterize the specific structural change. Not only the wild-type, but also the M467Q, which mutates the amino acid residue coordinating T1Cu, were precisely analyzed in terms of their molecular orbital levels, and the optimized redox potential of T1Cu was theoretically reconfirmed.