Structural requirements for bone sialoprotein binding and modulation of matrix metalloproteinase-2

Alka Jain, Abdullah Karadag, Larry W. Fisher, Neal S. Fedarko

Research output: Contribution to journalArticlepeer-review

Abstract

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 carboxyterminal domains of BSP contribute to restoration of activity to TIMP2-inhibited MMP-2, while the MMP-2 hemopexin domain is not required for reactivation.

Original languageEnglish (US)
Pages (from-to)10162-10170
Number of pages9
JournalBiochemistry
Volume47
Issue number38
DOIs
StatePublished - Sep 23 2008

ASJC Scopus subject areas

  • Biochemistry

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