Aluri Swathi, de Visser Sam P
The Manchester Interdisciplinary Biocenter and the School of Chemical Engineering and Analytical Science, The University of Manchester, Manchester M1 7DN, United Kingdom.
J Am Chem Soc. 2007 Dec 5;129(48):14846-7. doi: 10.1021/ja0758178. Epub 2007 Nov 10.
We present here the first density functional theoretic study into the mechanism of cysteine dioxygenation by a model of cysteine dioxygenase enzymes. A large active site model containing the ligands bound to iron plus amino acid residues that are involved in hydrogen bonding interactions with the substrate is used. The reaction takes place via multi-state reactivity patterns on competing singlet, triplet, and quintet spin states, whereby the latter is the ground state in most complexes. Several new intermediates have been predicted, which have not been anticipated before. The dioxygen-bound complex is in a singlet spin ground state, and a state crossing to the quintet spin state leads to an FeOOS ring structure that splits into a cysteinyloxide radical that reorients and abstracts an electron from the iron center. In the final step, the oxoiron donates the oxygen atom to the substrate to produce cysteine sulfinic acid in a highly exothermic process. The rate-determining step is the initial step in the reaction mechanism on the quintet spin state surface.
我们在此展示了对一种半胱氨酸双加氧酶模型催化半胱氨酸双加氧反应机制的首次密度泛函理论研究。使用了一个大型活性位点模型，该模型包含与铁结合的配体以及参与与底物形成氢键相互作用的氨基酸残基。反应通过在竞争的单重态、三重态和五重态自旋态上的多态反应模式进行，其中五重态在大多数配合物中是基态。预测了几种之前未曾预料到的新中间体。双氧结合的配合物处于单重态自旋基态，向五重态自旋态的态交叉导致形成一个FeOOS环结构，该结构分裂成一个半胱氨酸氧化物自由基，该自由基重新取向并从铁中心夺取一个电子。在最后一步，氧合铁将氧原子给予底物，在一个高度放热的过程中生成半胱氨酸亚磺酸。速率决定步骤是五重态自旋态表面反应机制中的初始步骤。
