Structural Requirements for Bone Sialoprotein Binding and Modulation of Matrix Metalloproteinase-2.
- Resource Type
- Article
- Authors
- Jain, Alka; Karadag, Abdullah; Fisher, Larry W.; Fedarko, Neal S.
- Source
- Biochemistry. 9/23/2008, Vol. 47 Issue 38, p10162-10170. 9p. 1 Chart, 7 Graphs.
- Subject
- *METALLOPROTEINASES
*METALLOENZYMES
*MATRICES (Mathematics)
*ENZYMES
*PEPTIDES
- Language
- ISSN
- 0006-2960
Bone sialoprotein (BSP) has been shown to induce limited gelatinase activity in latent matrix metalloproteinase-2 (MMP-2) without removal of the propeptide and to restore enzymatic activity to MMP-2 previously inhibited by tissue inhibitor of matrix metalloproteinase-2 (TIMP2). The current study identifies structural domains in human BSP and MMP-2 that contribute to these interactions. The 26 amino acid domain encoded by exon 4 of BSP is shown by a series of binding and activity assays to be involved in the displacement of MMP-2's propeptide from the active site and thereby inducing the protease activity. Binding assays in conjunction with enzyme activity assays demonstrate that both amino- and carboxy-terminal domains of BSP contribute to restoration of activity to TIMP2-inhibited MMP-2, while the MMP-2 hemopexin domain is not required for reactivation. [ABSTRACT FROM AUTHOR]