Endostatin binds to the catalytic domain of matrix metalloproteinase-2

• Published in: FEBS letters 2002-05, Vol.519 (1), p.147-152
• Main Authors: Lee, Seo-Jin, Jang, Jin-Wook, Kim, Young-Mi, Lee, Hyun Ick, Jeon, Jun Yung, Kwon, Young-Guen, Lee, Seung-Taek
• Format: Article
• Language: English
• Subjects: Active site; Animals; APMA, 4-aminophenylmercuric acetate; Catalytic domain; Catalytic Domain - physiology; Cell Line; Collagen - genetics; Collagen - metabolism; Endostatin; Endostatins; Enzyme Inhibitors - pharmacology; Enzyme Precursors - antagonists & inhibitors; Enzyme Precursors - genetics; Enzyme Precursors - metabolism; Gelatinases - antagonists & inhibitors; Gelatinases - genetics; Gelatinases - metabolism; HP, hemopexin-like; Humans; Hydroxamic Acids - pharmacology; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase Inhibitors; Metalloendopeptidases - antagonists & inhibitors; Metalloendopeptidases - genetics; Metalloendopeptidases - metabolism; Mice; MMP, matrix metalloproteinase; MMP-2; PBS, phosphate-buffered saline; Peptide Fragments - genetics; Peptide Fragments - metabolism; Protein Binding - physiology; Protein Structure, Tertiary - physiology; RU, response unit; Sequence Deletion; Spodoptera; SPR, surface plasmon resonance; Surface Plasmon Resonance; TIMP, tissue inhibitor of metalloproteinase; Tissue Inhibitor of Metalloproteinase-2 - genetics; Tissue Inhibitor of Metalloproteinase-2 - metabolism
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(02)02742-4

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.