An approach for visualization of the active site of enzymes with unknown three-dimensional structures

A new approach for virtual characterization of the active site structure of enzymes with unknown three-dimensional (3D) structure has been proposed. I t includes analysis of data on enzyme interaction with reversible competiti ve inhibitors, their 3D structures and moulding of the substrate-binding re gion. The superposition of ligands in biologically active conformations all ows to determine the shape and dimension of the active site cavity accommod ating these compounds. Monoamine oxidase A (MAO-A), a "typical" enzyme with unknown spatial organisation, was used to test this method. The correctnes s of such approach was validated by the analysis of HIV protease interactio n with its inhibitors using 3D structures of their complexes. Mould of the substrate/inhibitor binding site can be used for the visualization of this binding site and for searching new ligands in molecular databases.