Veselovsky A V, Medvedev A E, Tikhonova O V, Skvortsov V S, Ivanov A S
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow, 119832, Russia.
Biochemistry (Mosc). 2000 Aug;65(8):910-6.
The mold of the substrate-binding region of the active site of monoamine oxidase A (MAO A) was designed using data of the enzyme interaction with reversible competitive inhibitors and the analysis of their three-dimensional structures. The superposition of ligands in biologically active conformations allowed determination of the shape and dimension of the active site cavity accommodating these compounds. The correctness of this approach was validated by the analysis of HIV protease interaction with its inhibitors using three-dimensional structures of HIV protease-inhibitor complexes. The mold of the substrate/inhibitor-binding site can be used for searching for new ligands in molecular databases and the development of a new generation of MAO inhibitors using lead structures that have not been employed for this purpose yet.
利用单胺氧化酶A（MAO A）活性位点底物结合区域与可逆竞争性抑制剂的酶相互作用数据及其三维结构分析，设计了该区域的模型。配体在生物活性构象中的叠加使得能够确定容纳这些化合物的活性位点腔的形状和尺寸。通过使用HIV蛋白酶-抑制剂复合物的三维结构分析HIV蛋白酶与其抑制剂的相互作用，验证了该方法的正确性。底物/抑制剂结合位点的模型可用于在分子数据库中搜索新的配体，并利用尚未用于此目的的先导结构开发新一代MAO抑制剂。
