A heparin binding motif on the pro-domain of human procathepsin L mediates zymogen destabilization and activation.
Biochem Biophys Res Commun
; 366(3): 862-7, 2008 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-18086562
ABSTRACT
The molecular mechanism by which heparin modulates the processing of procathepsin L in the extracellular environment is proposed. We show that heparin reduces the stability of the pro form of cathepsin L at pH 5 by binding to a putative heparin binding motif (BBXB) in the pro-domain. Mutations to this motif on procathepsin L reduce heparin binding affinity and heparin-induced destabilization; in contrast, heparin only slightly destabilizes the mature cathepsin L domain. Gel analysis further shows that heparin makes procathepsin L a much better substrate for cathepsin L. Thus, heparin enhances the rate of zymogen activation by destabilization upon binding to the BBXB motif. Determining the mechanism by which procathepsin L is activated in the extracellular matrix is important to the understanding of the role that cathepsin L plays in tumour invasion.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Pichia
/
Cisteína Endopeptidases
/
Heparina
/
Catepsinas
/
Precursores Enzimáticos
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Reino Unido