title: 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-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 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.
authors.affiliation: National Research Laboratory of Cellular Biochemistry, Department of Biochemistry, College of Science, and Protein Network Research Center, Yonsei University, Seoul, Republic of Korea.
authors.forename: Seo Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Jang
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: Hyun Ick
authors.initials: HI
authors.lastname: Lee
authors.forename: Jun Yung
authors.initials: JY
authors.lastname: Jeon
authors.forename: Young Guen
authors.initials: YG
authors.lastname: Kwon
authors.forename: Seung Taek
authors.initials: ST
authors.lastname: Lee
mesh_terms: D000818:Animals; D020134:Catalytic Domain / Q000502:physiology; D002460:Cell Line; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D043169:Endostatins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D017384:Sequence Deletion; D018411:Spodoptera; D020349:Surface Plasmon Resonance; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D043169:Endostatins; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D010446:Peptide Fragments; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase; D020778:Matrix Metalloproteinase 2; C010531:actinonin