title: Structural requirements for bone sialoprotein binding and modulation of matrix metalloproteinase-2.
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 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.
authors: Johns Hopkins University School of Medicine, USA.
authors: Alka
authors: A
authors: Jain
authors: Abdullah
authors: A
authors: Karadag
authors: Larry W
authors: LW
authors: Fisher
authors: Neal S
authors: NS
authors: Fedarko
mesh_terms: D000595:Amino Acid Sequence; D004789:Enzyme Activation / Q000235:genetics; D004792:Enzyme Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics; D012795:Sialoglycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
chemical_list: D004792:Enzyme Precursors; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; D012795:Sialoglycoproteins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2