Patent ID: 7991601
Filing Date: 2011-08-02
Classification: C07K

Abstract:
1. A method of designing a potential modulator that selectively modulates the activity of a glucose regulated protein 94 kDa (GRP94) polypeptide, the method comprising: (a) obtaining a crystalline form of a GRP94 ligand binding domain polypeptide complex, wherein said GRP94 polypeptide comprises amino acids 48-316 of SEQ ID NO: 6 complexed with N-ethylcarboxamidoadenosine (NECA) and forms in space group C2 with unit cell parameters of a=99-89.9 Å, b=89.614 Å, c=63.066 Å and β=90.132° or in space group C222 (b) determining the three-dimensional structure of the crystalline form of the GRP94 ligand binding domain polypeptide from step (a); (c) analyzing the determined three-dimensional GRP94 ligand binding domain structure by inputting and displaying on a computer the atomic coordinates according to Tables 1-3 to assess the binding pocket dimensions and designing a modulator therefrom; and (d) synthesizing said modulator based on the three-dimensional structure of the crystalline form of the GRP94 ligand binding domain polypeptide, whereby a modulator that selectively modulates the activity of a GRP94 polypeptide is designed.