Brandt W, Lehmann T, Thondorf I, Born I, Schutkowski M, Rahfeld J U, Neubert K, Barth A
Biochemistry/Biotechnology Department, Martin-Luther-University of Halle-Wittenberg, Germany.
Int J Pept Protein Res. 1995 Dec;46(6):494-507. doi: 10.1111/j.1399-3011.1995.tb01605.x.
A molecular model of the active site of the serine protease dipeptidyl peptidase IV (DPP IV or CD26) has been developed on the basis of comparative molecular field analysis (CoMFA) of competitive inhibitors and by force field calculations. By application of CoMFA experimentally obtained inhibition constants Ki have been successfully predicted. The resulting steric and electrostatic coefficients of CoMFA were used for the development of the molecular model. The main assumptions of the model are the recognition of substrates or inhibitors by the side chains of a tyrosine (S1-position) and a tryptophan residue (S2-position). The model helps us to understand a multitude of experimental data regarding the substrate specificity of this enzyme as well as results obtained by genetic engineering experiments by other authors. General conclusions concerning a new family of serine proteases are drawn and discussed.
基于竞争性抑制剂的比较分子场分析（CoMFA）并通过力场计算力场计算，已构建了丝氨酸蛋白酶二肽基肽酶IV（DPP IV或CD26）活性位点的分子模型。通过应用CoMFA，已成功预测了实验获得的抑制常数Ki。CoMFA所得的空间和静电系数被用于分子模型的构建。该模型的主要假设是酪氨酸（S1位）和色氨酸残基（S2位）的侧链对底物或抑制剂的识别。该模型有助于我们理解关于该酶底物特异性的大量实验数据，以及其他作者通过基因工程实验获得的结果。得出并讨论了关于丝氨酸蛋白酶新家族的一般性结论。
