Probing the active sites of monoamine oxidase A and B with 1,4-disubstituted tetrahydropyridine substrates and inactivators.
Probing the active sites of monoamine oxidase A and B with 1,4-disubstituted tetrahydropyridine substrates and inactivators.
复制标题
使用 1,4-二取代四氢吡啶底物和灭活剂探测单胺氧化酶 A 和 B 的活性位点。
DOI：
10.1021/jm970079r
复制
发表时间：
1997
期刊：
影响因子：
--
通讯作者：
CastagnoliJr,N
中科院分区：
文献类型：
--
作者：
Palmer,SL;Mabic,S;CastagnoliJr,N
为了更全面地表征单胺氧化酶（MAO） A和B活性位点的结构特征，我们研究了几种1-甲基和1-环丙基-4-芳基-1,2,3,6-四氢吡啶衍生物与人类胎盘A和牛肝B形式的酶的底物和抑制剂特性。我们发现4-（2-苯基苯基）类似物23对MAO-A具有较高的活性和选择性，而4-（3-苯基苯基）类似物22仅对MAO-B具有活性。在一系列基于n -环丙基机理的失活剂上观察到与n -甲基系列相似的选择性。这些结果支持了一项拓扑分析，该分析试图确定与这两种黄蛋白的底物和抑制剂选择性相关的立体因子，并提供了两种酶活性位点大小的更好定义。
As part of our efforts to characterize more fully the structural features of the monoamine oxidase (MAO) A and B active sites, we have examined the substrate and inhibitor properties of several 1-methyl- and 1-cyclopropyl-4-aryl-1,2,3,6-tetrahydropyridine derivatives with the human placental A and beef liver B forms of the enzyme. We find that the 4-(2-phenylphenyl) analog23exhibits a high activity and selectivity for MAO-A while the 4-(3-phenylphenyl) analog22shows activity only with MAO-B. Selectivities similar to those of theN-methyl series are observed with a series ofN-cyclopropyl mechanism based inactivators. These results support a topological analysis which attempts to identify steric factors related to the reported substrate and inhibitor selectivities of these two flavoproteins and provide a better definition of the size of the active sites of the two enzymes.