Endostatin binds to the catalytic domain of matrix metalloproteinase-2

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-2DeltaHP lacking the hinge and hemopexin-like (HP) domains bound little to the immobilized endostatin. The active MMP-2 and MMP-2DeltaHP, but not the HP domain of MMP-2, bound to endostatin at similar levels. In addition, preincubation of MMP-2 and MMP-2DeltaHP with the MMIP 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 MMP2. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.