Repič Matej, Purg Miha, Vianello Robert, Mavri Janez
Laboratory for Biocomputing and Bioinformatics, National Institute of Chemistry , Hajdrihova 19, SI-1000 Ljubljana, Slovenia.
J Phys Chem B. 2014 Apr 24;118(16):4326-32. doi: 10.1021/jp500795p. Epub 2014 Apr 11.
Monoamine oxidases (MAO) A and B are important flavoenzymes involved in the metabolism of amine neurotransmitters. Orru et al. ( J. Neural Transm. 2013 , 120 , 847 - 851 ) recently presented experimental results that have challenged the prevailing assumption that MAO A and MAO B employ an identical catalytic mechanism. We compared the spatial configuration of ionizable groups in both isozymes and estimated the time-averaged electrostatic potential by calculating the pKa values of five active site residues. Superimposition of both experimental structures shows very close overlap and the RMSD in placements of ionizable groups within 16 Å of the reaction center is only 0.847 Å. This similarity is also reflected in the calculated pKa values, where the largest difference between the MAO A and MAO B pKa values was found for residues Tyr188 in MAO B and the corresponding Tyr197 in MAO A assuming 1.23 units. The pKa values for the other four studied residues differ by less than 0.75 units. The results show that the electrostatic preorganizations in both active sites are very similar, supporting the idea that both enzymes work by the same mechanism.
单胺氧化酶（MAO）A和B是参与胺类神经递质代谢的重要黄素酶。奥鲁等人（《神经传递杂志》，2013年，第120卷，第847 - 851页）最近公布的实验结果对MAO A和MAO B采用相同催化机制这一普遍假设提出了挑战。我们比较了两种同工酶中可电离基团的空间构型，并通过计算五个活性位点残基的pKa值来估计时间平均静电势。两种实验结构的叠加显示出非常紧密的重叠，反应中心16 Å范围内可电离基团位置的均方根偏差（RMSD）仅为0.847 Å。这种相似性也反映在计算出的pKa值中，假设差值为1.23个单位，MAO B中的Tyr188残基与MAO A中相应的Tyr197残基的pKa值差异最大。其他四个研究残基的pKa值差异小于0.75个单位。结果表明，两个活性位点的静电预组织非常相似，支持了两种酶通过相同机制起作用的观点。
