Wetmore Stacey D, Smith David M, Bennett Justine T, Radom Leo
Research School of Chemistry, Australian National University, Canberra, ACT 0200, Australia.
J Am Chem Soc. 2002 Nov 27;124(47):14054-65. doi: 10.1021/ja027579g.
Ab initio molecular orbital calculations are used to examine the mechanism of action of B(12)-dependent ethanolamine ammonia-lyase involving the conversion of 2-aminoethanol to acetaldehyde plus ammonia. We attempt to elucidate the mechanism by which the enzyme facilitates this reaction through interactions between active-site residues and the substrate. Our calculations suggest a preferred pathway involving a 1,2-shift in the associated radical and also suggest that interactions between the enzyme and the migrating group of the substrate that afford an almost fully protonated migrating group will lead to the most efficient catalysis. However, this criterion on its own is insufficient to fully understand the rearrangement. Additional synergistic interactions between the spectator hydroxyl group in the substrate and active-site residues on the enzyme are required to lower the barrier height to a value consistent with experimental observations.
从头算分子轨道计算用于研究依赖维生素B12的乙醇胺氨裂合酶的作用机制，该机制涉及2-氨基乙醇转化为乙醛和氨。我们试图阐明该酶通过活性位点残基与底物之间的相互作用促进此反应的机制。我们的计算表明了一种涉及相关自由基1,2-迁移的优选途径，并且还表明酶与底物迁移基团之间的相互作用会使迁移基团几乎完全质子化，这将导致最有效的催化作用。然而，仅这一标准不足以完全理解重排过程。底物中的旁观羟基与酶上的活性位点残基之间还需要额外的协同相互作用，以将势垒高度降低到与实验观察结果一致的值。
