Reference : The matrix metalloproteinase 9 (mmp-9) hemopexin domain is a novel gelatin binding do...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
The matrix metalloproteinase 9 (mmp-9) hemopexin domain is a novel gelatin binding domain and acts as an antagonist
Roeb, E. [> >]
Schleinkofer, K. [> >]
Kernebeck, T. [> >]
Pötsch, S. [> >]
Jansen, B. [> >]
Behrmann, Iris mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Matern, S. [> >]
Grötzinger, J. [> >]
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
Yes (verified by ORBilu)
[en] Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Animals ; Binding Sites ; Cells, Cultured ; Circular Dichroism ; Cloning, Molecular ; Gelatin ; Glutathione Transferase ; Hemopexin ; Kinetics ; Matrix Metalloproteinase 9 ; Mice ; Molecular Sequence Data ; Peptide Fragments ; Recombinant Fusion Proteins ; Amino Acid Sequence
[en] Matrix metalloproteinases (MMPs) are involved in the remodeling processes of the extracellular matrix and the basement membrane. Most MMPs are composed of a regulatory, a catalytic, and a hemopexin subunit. In many tumors the expression of MMP-9 correlates with local tumor growth, invasion, and metastasis. To analyze the role of the hemopexin domain in these processes, the MMP-9 hemopexin domain (MMP-9-PEX) was expressed as a glutathione S-transferase fusion protein in Escherichia coli. After proteolytic cleavage, the isolated PEX domain was purified by size exclusion chromatography. In a zymography assay, MMP-9-PEX was able to inhibit MMP-9 activity. The association and dissociation rates for the interaction of MMP-9-PEX with gelatin were determined by plasmon resonance. From the measured rate constants, the dissociation constant was calculated to be K(d) = 2,4 x 10(-8) m, demonstrating a high affinity between MMP-9-PEX and gelatin. In Boyden chamber experiments the recombinant MMP-9-PEX was able to inhibit the invasion of melanoma cells secreting high amounts of MMP-9 in a dose-dependent manner. These data demonstrate for the first time that the hemopexin domain of MMP-9 has a high affinity binding site for gelatin, and the particular recombinant domain is able to block MMP-9 activity and tumor cell invasion. Because MMP-9 plays an important role in metastasis, this antagonistic effect may be utilized to design MMP inhibition-based cancer therapy.

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