Godfrey Elizabeth, Porro Cristina S, de Visser Sam P
The Manchester Interdisciplinary Biocenter and the School of Chemical Engineering and Analytical Science, The University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom.
J Phys Chem A. 2008 Mar 20;112(11):2464-8. doi: 10.1021/jp710999v. Epub 2008 Feb 1.
We present here the first quantum mechanical/molecular mechanics (QM/MM) studies of taurine/alpha-ketoglutarate dioxygenase (TauD) enzymes. Our studies are focused on the chemical properties of the oxo-iron species and the effect of the protein environment on its structural and electronic behavior. Although the active site region of TauD is very polar with many key hydrogen bonding interactions and salt bridges, the actual effect of the protein environment on the ordering and relative energies of the possible spin state structures is found to be quite small. Optimized geometries are very close to ones observed with density functional theory models that did not take the protein environment into consideration. The calculations show that protonation of the histidine ligands of iron is essential to reproduce the correct electronic representations of the enzyme. Hydroxylation studies of taurine by the oxo-iron active species predict that it is a very efficient catalyst that reacts with substrates via low reaction barriers.
我们在此展示了对牛磺酸/α-酮戊二酸双加氧酶（TauD）的首次量子力学/分子力学（QM/MM）研究。我们的研究聚焦于氧代铁物种的化学性质以及蛋白质环境对其结构和电子行为的影响。尽管TauD的活性位点区域极性很强，存在许多关键的氢键相互作用和盐桥，但发现蛋白质环境对可能的自旋态结构的有序性和相对能量的实际影响相当小。优化后的几何结构与未考虑蛋白质环境的密度泛函理论模型所观察到的结构非常接近。计算表明，铁的组氨酸配体的质子化对于重现该酶正确的电子表示至关重要。氧代铁活性物种对牛磺酸的羟基化研究预测，它是一种非常高效的催化剂，通过低反应势垒与底物发生反应。
