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Cysteine proteinase activity regulation. A possible role of heparin and heparin-like glycosaminoglycans.
Almeida, P C; Nantes, I L; Rizzi, C C; Júdice, W A; Chagas, J R; Juliano, L; Nader, H B; Tersariol, I L.
Afiliación
  • Almeida PC; Centro Interdisciplinar de Investigação Bioquímica, Universidade Mogi das Cruzes, Prédio II, Brazil.
J Biol Chem ; 274(43): 30433-8, 1999 Oct 22.
Article en En | MEDLINE | ID: mdl-10521421
Papain is considered to be the archetype of cysteine proteinases. The interaction of heparin and other glycosaminoglycans with papain may be representative of many mammalian cysteine proteinase-glycosaminoglycan interactions that can regulate the function of this class of proteinases in vivo. The conformational changes in papain structure due to glycosaminoglycan interaction were studied by circular dichroism spectroscopy, and the changes in enzyme behavior were studied by kinetic analysis, monitored with fluorogenic substrate. The presence of heparin significantly increases the alpha-helix content of papain. Heparin binding to papain was demonstrated by affinity chromatography and shown to be mediated by electrostatic interactions. The incubation of papain with heparin promoted a powerful increase in the affinity of the enzyme for the substrate. In order to probe the glycosaminoglycan structure requirements for the papain interaction, the effects of two other glycosaminoglycans were tested. Like heparin, heparan sulfate, to a lesser degree, was able to decrease the papain substrate affinity, and it simultaneously induced alpha-helix structure in papain. On the other hand, dermatan sulfate was not able to decrease the substrate affinity and did not induce alpha-helix structure in papain. Heparin stabilizes the papain structure and thereby its activity at alkaline pH.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cisteína Endopeptidasas / Heparina / Papaína / Glicosaminoglicanos Idioma: En Revista: J Biol Chem Año: 1999 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cisteína Endopeptidasas / Heparina / Papaína / Glicosaminoglicanos Idioma: En Revista: J Biol Chem Año: 1999 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos