LOCALIZATION OF THE IMIDAZOLINE BINDING DOMAIN ON MONOAMINE-OXIDASE-B

Monoamine oxidase B (MAO-B) was recently identified as a member of the family of imidazoline binding proteins, To localize the imidazoline b inding domain on MAO-B, we labeled the domain with the imidazoline pho toaffinity adduct [I-125]2-(3-azido-4-iodophenoxy)methylimidazoline in rat and human liver and visualized labeled peptides by autoradiograph y/sodium dodecyl sulfate-polyacrylamide gel electrophoresis after CNBr cleavage of the labeled protein, Based on species-specific fragmentat ion patterns and immunoprecipitation of labeled peptides, the imidazol ine binding domain was localized to residues K149 to M222 of human MAO -B. The imidazoline binding domain is encompassed within a region that influences substrate processing but is distinct from primary sites of interaction for the enzyme inhibitors pargyline and lazabemide (Ro 19 -6327). Radioligand binding assays and photoaffinity labeling also ind icated that the various classes of compounds did not cross-compete at the different enzyme domains. Identification of an imidazoline binding domain on MAO-B provides a new opportunity for the potential pharmaco logical development of imidazoline/guanidinium compounds and also pres ents additional avenues for structure/function analysis of the monoami ne oxidase enzymes.