In vitro reconstitution of proMatrix Metalloproteinase-9/Chondroitin Sulfate Proteoglycan Complexes. Identification of motifs in proMMP-9 and the serglycin core protein involved in the complex formation.
Previously it has been shown that different monocytic leukemic cell lines such as THP-1, MonoMac and U-937 can produce proteolytic enzymes such as MMP-9 as well as various types of proteoglycans (PG). These proteins have been shown to be involved in homeostasis as well as in various diseases, such as cancer. When proMMP-9 was mixed with isolated PGs from these three cell lines or pure serglycin and versican, proMMP-9/PG complexes were formed which alters several important properties of this protease. Different PGs and proteins secreted from THP-1 and MonoMac cells were partly separated by the use of size exclusion chromatography. Fractions with isolated PGs could to various extents form proMMP-9/PG complexes in vitro and the largest amount of complex was formed in fractions with large amounts of serglycin. Also other unidentified PGs or PG-associated proteins could form complexes with proMMP-9. These complexes are putative drug targets. In this thesis, motifs and amino acids in proMMP-9 and in the serglycin core protein that is involved in complex formation between the two molecules have also been identified. This knowledge can be used in the future to develop drugs that bind to specific sequences in MMP-9 and act as highly specific protease inhibitors.
PublisherUiT Norges arktiske universitet
UiT The Arctic University of Norway
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