Structural model of the catalytic domain of an enzyme with cell adhesion activity: human vascular adhesion protein-1 (HVAP-1) D4 domain is an amine oxidase

Human vascular adhesion protein-1 (HVAP-1) is a multifunctional protein hav ing at least two different cellular roles, functioning both as a lymphocyte -endothelial cell adhesion protein and as an enzyme with monoamine oxidase activity. HVAP-1 is a 180 kDa homodimeric glycoprotein consisting of a memb rane-spanning domain and three predicted extracellular copper-containing am ine oxidase domains. In HVAP-1 the extracellular domains are composed of a large domain DJ, containing the active site and forming the interface of th e dimer, while the smaller D2 and D3 domains surround the D4 dimer near the entrance to the active site. The structural model of the catalytic D4 doma in of HVAP-1 reveals that all components necessary for enzymatic monoamine oxidase activity are indeed present within the HVAP-1 and pinpoints residue s that may be key to substrate entry through a channel to the active site a nd residues likely to be involved in substrate specificity as well as struc tural features critical to dimer formation. Proper glycosylation is require d for the cell adhesion function of HVAP-1 and the predicted location of th e sugar units at the solvent-exposed surface suits this function well.