Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, Kentucky 40536, USA.
J Phys Chem B. 2011 Jul 14;115(27):8797-805. doi: 10.1021/jp112030p. Epub 2011 Jun 17.
Butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) are highly homologous proteins with distinct substrate preferences. In this study we compared the active sites of monomers and tetramers of human BChE and human AChE after performing molecular dynamics (MD) simulations in water-solvated systems. By comparing the conformational dynamics of gating residues of AChE and BChE, we found that the gating mechanisms of the main door of AChE and BChE are responsible for their different substrate specificities. Our simulation of the tetramers of AChE and BChE indicates that both enzymes could have two dysfunctional active sites due to their restricted accessibility to substrates. The further study on catalytic mechanisms of multiple forms of AChE and BChE would benefit from our comparison of the active sites of the monomers and tetramers of both enzymes.
丁酰胆碱酯酶（BChE）和乙酰胆碱酯酶（AChE）是具有不同底物偏好的高度同源蛋白。在这项研究中，我们在水溶剂化系统中进行分子动力学（MD）模拟后，比较了人 BChE 和人 AChE 的单体和四聚体的活性部位。通过比较 AChE 和 BChE 的门控残基的构象动力学，我们发现 AChE 和 BChE 的主门的门控机制负责它们不同的底物特异性。我们对 AChE 和 BChE 的四聚体的模拟表明，由于它们对底物的限制可及性，两种酶都可能具有两个功能失调的活性部位。对 AChE 和 BChE 的多种形式的催化机制的进一步研究将受益于我们对两种酶的单体和四聚体的活性部位的比较。
