Cathepsin B activity regulation - Heparin-like glycosaminoglycans protect human cathepsin B from alkaline pH-induced inactivation

Cathepsin B activity regulation - Heparin-like glycosaminoglycans protect human cathepsin B from alkaline pH-induced inactivation

Author Almeida, P. C. Google Scholar
Nantes, I. L. Google Scholar
Chagas, Jair Ribeiro Autor UNIFESP Google Scholar
Rizzi, CCA Google Scholar
Faljoni-Alario, A. Google Scholar
Carmona, E. Google Scholar
Juliano, Luiz [UNIFESP Google Scholar
Nader, Helena Bonciani Autor UNIFESP Google Scholar
Tersariol, Ivarne Luis dos Santos Autor UNIFESP Google Scholar
Institution Univ Mogi das Cruzes
Universidade de São Paulo (USP)
Inst Butanta
Universidade Federal de São Paulo (UNIFESP)
Abstract It has been shown that lysosomal cysteine proteinases, specially cathepsin B, has been implicated in a variety of diseases involving tissue remodeling states, such as inflammation, parasite infection, and tumor metastasis, by degradation of extracellular matrix components. Recently, we have shown that heparin and heparan sulfate bind to papain specifically; this interaction induces an increase of its alpha -helix content and stabilizes the enzyme structure even at alkaline pH (Almeida, P. C., Nantes, I. L,, Rizzi, C, C. A., Judice, W.A.S., Chagas, J. R., Juliano, L., Nader, H. B., and Tersariol, I. L. S. (1999) J. Biol. Chem. 274, 30433-30438). in the present work, a combination of circular dichroism analysis, affinity chromatography, cathepsin B mutants, and fluorogenic substrate assays were used to characterize the interaction of human cathepsin B with glycosaminoglycans. the nature of the cathepsin B-glycosaminoglycans interaction was sensitive to the charge and type of polysaccharide, Like papain, heparin and heparan sulfate bind cathepsin B specifically, and this interaction reduces the loss of cathepsin B alpha -helix content at alkaline pH. Our data show that the coupling of cathepsin B with heparin or heparan sulfate can potentiate the endopeptidase activity of the cathepsin B, increasing B-fold the half-life (t(1/2)) of the enzyme at alkaline pH, Most of these effects are related to the interaction of heparin and heparan sulfate with His(111) residue of the cathepsin B occluding loop. These results strongly suggest that heparan sulfate may be an important binding site for cathepsin B at cell surface, reporting a novel physiological role for heparan sulfate proteoglycans.
Language English
Date 2001-01-12
Published in Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 276, n. 2, p. 944-951, 2001.
ISSN 0021-9258 (Sherpa/Romeo, impact factor)
Publisher Amer Soc Biochemistry Molecular Biology Inc
Extent 944-951
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000166430900013

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