Paradoxical interactions between modifiers and elastase-2.
The serine endopeptidase elastase-2 from human polymorphonuclear leukocytes is associated with physiological remodeling and pathological degradation of the extracellular matrix. Glycosaminoglycans bound to the matrix or released after proteolytic processing of the core proteins of proteoglycans are potential ligands of elastase-2. In vitro, this interaction results in enzyme inhibition at low concentrations of glycosaminoglycans. However, inhibition is reversed and even abolished at high concentrations of the ligands. This behavior, which can be interpreted by a mechanism involving at least two molecules of glycosaminoglycan binding the enzyme at different sites, may cause interference with the natural protein inhibitors of elastase-2, particularly the alpha-1 peptidase inhibitor. Depending on their concentration, glycosaminoglycans can either stimulate or antagonize the formation of the enzyme-inhibitor complex and thus affect proteolytic activity. This interference with elastase-2 inhibition in the extracellular space may be part of a finely-tuned control mechanism in the microenvironment of the enzyme during remodeling and degradation of the extracellular matrix.
Schenker
Patricia
P
Department of Biochemistry, University of Zurich, Zurich, Switzerland.
Baici
Antonio
A
D000818:Animals; D002809:Chondroitin Sulfates / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000201:enzymology; D005110:Extracellular Space / Q000201:enzymology; D006025:Glycosaminoglycans / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D009504:Neutrophils / Q000201:enzymology; D011134:Polysaccharides / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000097:blood* / Q000737:chemistry; D013431:Sulfates / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006025:Glycosaminoglycans; D011134:Polysaccharides; D011506:Proteins; D013431:Sulfates; C028656:eglin proteinase inhibitors; D002809:Chondroitin Sulfates; D012697:Serine Endopeptidases; C117309:pancreatic elastase II