Endostatin binds to the catalytic domain of matrix metalloproteinase‐2

Abstract
We previously reported that endostatin inhibits endothelial and tumor cellular invasion by blocking activation and catalytic activity of matrix metalloproteinase (MMP)‐2. Here we have examined the domain of proMMP‐2 responsible for the binding of endostatin using surface plasmon resonance. ProMMP‐2 and proMMP‐2ΔHP lacking the hinge and hemopexin‐like (HP) domains bound little to the immobilized endostatin. The active MMP‐2 and MMP‐2ΔHP, but not the HP domain of MMP‐2, bound to endostatin at similar levels. In addition, preincubation of MMP‐2 and MMP‐2ΔHP with the MMP inhibitor actinonin, which binds to the active site of MMP‐2, abolished their bindings to endostatin. These results indicate that endostatin binds to neither the latent proMMP‐2 nor the HP domain but to the catalytic domain of MMP‐2.