Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed a procedure for the use of minislab gels to electrophoretically separate proteoglycans (PGs), large macromolecules with molecular masses greater than 2.5 million Da. Our procedure is a modification of the method of C.A. McDevitt and H. Muir (Anal. Biochem. 44, 612-622, 1971) for agarose/polyacrylamide, composite tube gels. These 1% agarose/1.2% acrylamide minigels are run at 35 mA for 75 min; bands are visualized by toluidine blue staining. The subtle size differences between the large aggregating PGs isolated from rat chondrosarcoma, bovine nasal septal cartilage, and adult bovine articular cartilage (which consists of two subpopulations) can be distinguished by their migration on these large pore gels. Chondroitin sulfate chains, added to all wells as a marker of constant mobility, ran immediately behind the dye front. The distance of migration into the gel of PGs incubated overnight with cathepsin B, carboxypeptidase A, papain, plasmin, elastase, or cathepsin G varied with the size of the cleavage products. We propose the use of this procedure for a convenient assessment of cartilage PGs and a rapid, reproducible assay for proteoglycanase activity.
 ...
PMID:Agarose/polyacrylamide minislab gel electrophoresis of intact cartilage proteoglycans and their proteolytic degradation products. 178 94

Platinum compounds are among the most used DNA-damaging anticancer drugs, however they can also be tailored to target biological substrates different from DNA, for instance enzymes involved in cancer progression. We recently reported that some platinum complexes with three labile ligands inhibit matrix metalloproteinase activity in a selective way. We have now extended the investigation to a series of platinum complexes having three chlorido or one chlorido and a dimethylmalonato leaving ligands. All compounds are strong inhibitors of MMP-3 by a noncompetitive mechanism, while platinum drugs in clinical use are not. Structural investigations reveal that the platinum substrate only loses two labile ligands, which are replaced by an imidazole nitrogen of His224 and a hydroxyl group, while it retains one chlorido ligand. A chlorido and a hydroxyl group are also present in the zinc complex inhibitor of carboxypeptidase A, whose active site has strong analogies with that of MMP-3.
 ...
PMID:Mechanistic insight into the inhibition of matrix metalloproteinases by platinum substrates. 1975 21