Interactions between human extracellular superoxide dismutase C and sulfated polysaccharides.
The high heparin affinity subtype C of the secretory enzyme extracellular superoxide dismutase (EC-SOD) exists in the body mainly complexed with extracellular sulfated glycosaminoglycans (SGAGs). Addition of sulfated polysaccharides to EC-SOD C resulted in a prompt partial inhibition of the enzymic activity, in most cases amounting to 10-17%, but with the large dextran sulfate 500,000 amounting to 35%. Complex formation between heparin and EC-SOD C could also be observed as increases in apparent molecular weight of the enzyme. The findings suggest that the binding sites for SGAGs on EC-SOD C are localized far from the active site and that EC-SOD in vivo associated with SGAGs should retain the major part of its enzymic activity. Studies with amino acid-specific reagents suggested that both lysine and arginine residues are involved in the binding of SGAGs. In particular, modification of only a few lysine residues/subunit resulted in loss of high SGAG affinity, whereas arginine modification resulted in loss of not only SGAG affinity but also enzymic activity. We propose that this is due to modification of Arg-186, which is homologous to the highly conserved arginine in the entrance to the active site of the copperzinc-SODs.
Adachi
T
T
Department of Clinical Chemistry, Umeå University Hospital, Sweden.
Marklund
S L
SL
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002417:Cattle; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D011748:Pyrogallol / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000097:blood / Q000378:metabolism*; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology
D003911:Dextrans; D006025:Glycosaminoglycans; D007527:Isoenzymes; D011994:Recombinant Proteins; D011748:Pyrogallol; D014302:Trinitrobenzenesulfonic Acid; D006493:Heparin; D016264:Dextran Sulfate; D013482:Superoxide Dismutase