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.
Bibliographical noteFunding Information:
We thank Dr. Y.-M. Kim for thoughtful discussions. This work was supported by grants from the NRL program of MOST NRDP (2000-N-NL-01-C-244), MOST/KOSEF through PNRC at Yonsei University (R11-2000-006102-0) (to S.-T. L.), and MOHW (01-PJ1-PG1-01CH04-005) (to Y.-G. K.).
All Science Journal Classification (ASJC) codes
- Structural Biology
- Molecular Biology
- Cell Biology