Editor-in-Chief: Brüne, Bernhard
Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred
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Substrate Specificity and Inhibitor Studies of a Membrane-Bound Ganglioside Sialidase Isolated from Human Brain Tissue
Citation Information: Biological Chemistry. Volume 383, Issue 11, Pages 1735–1742, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2002.194, June 2005
- Published Online:
A gangliosidespecific sialidase that controls cellular functions such as growth, differentiation, and adhesion has been observed in a variety of cells, but its characterization proved difficult due to firm membrane attachment and lability of the purified enzyme. Here we report on the specificity toward gangliosides and susceptibility to certain inhibitors of a ganglioside sialidase solubilized and purified 5100-fold from human brain. The sialidase removed terminal sialic acids from gangliosides GM3, GM4, GD3, GD2, GD1a, GD1b, GT1b and GQ1b, but was inactive toward gangliosides with sialic acid in a branching position (as in GM1 and GM2). LysoGM3 and GD1a were good substrates, too, whereas Oacetylation of the sialic acid as in 9-OacetylGD3 caused strongly reduced cleavage. The new influenza virus drug 4-guanidino-2-deoxy-2,3- dehydroNacetylneuraminic acid (Zanamivir) exhibited an IC50 value of about 710 5 M that was in the range of the classical sialidase inhibitor 2-deoxy-2,3-dehydro Nacetylneuraminic acid; the bacterial sialidase inhibitor 4-nitrophenyloxamic acid, however, was ineffective. The glycosaminoglycans heparan sulfate, heparin, chondroitin sulfates A and B, as well as dextran sulfate and suramin, were all strongly inhibitory, suggesting that glycosaminoglycans present on the cell surface or in the extracellular matrix may influence the ability of the sialidase to alter the ganglioside composition of the membrane.
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