Googheri Mohammad Sadegh Sadeghi, Housaindokht Mohammad Reza, Sabzyan Hassan
Biophysical chemistry laboratory, Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Biophysical chemistry laboratory, Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran; Research and Technology Center of Biomolecules, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
J Mol Graph Model. 2014 Nov;54:131-40. doi: 10.1016/j.jmgm.2014.10.001. Epub 2014 Oct 22.
Candida Antarctica lipase B (CALB), a specific enzyme to catalyze the hydrolysis of esters, can be a good candidate for acetylcholine (ACh) hydrolysis instead of acetylcholinesterase. The catalytic mechanism of the CALB acylation, as the first stage in the hydrolysis reaction, with ACh and methylcaprylate (MEC) has been examined by using density functional theory technique. The significant emphasis of this article is on the free energy barriers for the acylation step of hydrolysis reactions. Computed free energy barriers of the first step are 9.2 and 15.9 kcal mol(-1), but for the second step are 7.9 and 11.6 kcal mol(-1) for MEC and ACh respectively. Activation free energies are in the comparable and acceptable range and imply both of two reactions are theoretically possible. The stability role of the adjacent amino acids was examined by using two applied tools. It is exposed that the oxyanion hole residues decrease energy barriers by stabilizing the transition state structures.
南极假丝酵母脂肪酶B（CALB）是一种催化酯水解的特异性酶，它可以替代乙酰胆碱酯酶，成为水解乙酰胆碱（ACh）的良好候选酶。利用密度泛函理论技术研究了CALB酰化反应（作为水解反应的第一步）与ACh和甲基辛酸酯（MEC）的催化机制。本文重点关注水解反应酰化步骤的自由能垒。计算得出第一步的自由能垒分别为9.2和15.9千卡/摩尔，但第二步中，MEC和ACh的自由能垒分别为7.9和11.6千卡/摩尔。活化自由能在可比且可接受的范围内，这意味着这两个反应在理论上都是可能的。通过使用两种应用工具研究了相邻氨基酸的稳定性作用。结果表明，氧负离子空穴残基通过稳定过渡态结构降低了能垒。
