Modeling of substrate-binding region of the active site of monoamine oxidase A

The mold of the substrate-binding region of the active site of monoamine ox idase A (MAO A) was designed using data of the enzyme interaction with reve rsible competitive inhibitors and the analysis of their three-dimensional s tructures. The superposition of ligands in biologically active conformation s allowed determination of the shape and dimension of the active site cavit y accommodating these compounds. The correctness of this approach was valid ated 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 l igands in molecular data-bases and the development of a new generation of M AO inhibitors using lead structures that have not been employed for this pu rpose yet.