Prohormone/proprotein-proteinase crystal structure and use thereof

摘要

Space form of a polypeptide (I) that is at least one fragment, of at least 50 amino acids (aa), from a protein (II) of the prohormone/proprotein convertase (PC) family, or its derivatives. Independent claims are also included for the following: (1) crystal (C) that contains, per asymmetric unit in the unit cell, at least one polypeptide (PP) and optionally at least one additional compound (X) where PP has the new space form; (2) method for preparing (C) where the space group of the crystal is monoclinic, tetragonal, orthorhombic, cubic, triclinic, hexagonal or trigonal/rhombohedral; (3) compounds (Y), functioning as ligands, that bind PCs or related proteins; (4) methods for identifying compounds (Z) that inhibit the physiological, particularly endoprotease, activity of a PC, especially furin; (5) (Z) identified by methods (4); (6) method for representing the three-dimensional (3D) structure of a polypeptide of unknown structure, containing at least one sequence, or its derivative, from a PC, or a complex that contains such a polypeptide, by determining the structure on the basis of one of the new space forms; (7) method for identifying compounds (Z1) that inhibit the physiological activity of a polypeptide of unknown structure, containing at least one fragment of at least 50 aa from a PC protein or its derivative; (8) machine-readable data storage medium that contains the structural coordinates of a PC, especially furin, or its homolog; (9) method for obtaining structural information about a molecule, or complex, of unknown structure using the coordinates of a PC protein; and (10) set of structural coordinates of a PC protein, or a fragment of it. ACTIVITY : Cytostatic; Antibacterial; Virucide; Anti-HIV; Immunosuppressant; Antiinflammatory. No details of tests for these activities are given. MECHANISM OF ACTION : Inhibiting endoprotease activity of prohormone/propeptide convertases.