Abstract: The present invention relates to polypeptides which comprise the ligand binding domain of Tie-2, crystalline forms of these polypeptides and the use of these crystalline forms to determine the three dimensional structure of the catalytic domain of Tie-2. The invention also relates to the use of the three dimensional structure of the Tie-2 catalytic domain both alone, or in complex with inhibitors, in methods of designing and/or identifying potential inhibitors of Tie-2 activity, for example, compounds which inhibit the binding of a native substrate to the Tie-2 catalytic domain.