alpha(1)-antichymotrypsin and kallistatin hydrolysis by human cathepsin D

alpha(1)-antichymotrypsin and kallistatin hydrolysis by human cathepsin D

Autor Pimenta, D. C. Google Scholar
Chen, V. C. Google Scholar
Chao, J. Google Scholar
Juliano, M. A. Google Scholar
Juliano, L. Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Med Univ S Carolina
Resumo In the present paper, we demonstrate that alpha (1)-antichymotrypsin, a serpin with high inhibitory specificity toward cathepsin G, and kallistatin, a human serpin with high specificity toward tissue kallikrein, are digested by cathepsin D, alpha (1)-Antichymotrypsin was hydrolyzed essentially in the reactive center loop at LS, A-L, or L-V bonds; kallistatin was split into small fragments, but we detected the cleavage at F-F and F-S bonds in its reactive center loop in the first 15 min of digestion. in contrast to alpha (1)-antichymotrypsin, kallistatin is irreversibly inactivated at pH 4.0. Synthetic internally quenched fluorescent peptides containing sequences similar to the reactive center loops of these serpins were hydrolyzed by cathepsin D. the peptides derived from kallistatin were hydrolyzed more efficiently, and particularly relevant was the high susceptibility of the substrates Abz-AIKFFSAQTNRHILRFNRQ-EDDnp (K-m = 0.08 muM, k(cat) = 2.4 s(-1)) and Abz-AIKFFSAQTNRQ-EDDnp (K-m = 0.8 muM. k(cat) = 17.8 s(-1)), which were hydrolyzed at the F-F bond. Therefore, besides the description of a new class of very efficient internally quenched substrates for cathepsin D, we give evidence for the downregulation role of this proteinase on alpha (1)-antichymobypsin and kallistatin. the acidification of extracellular milieu by tumor cells can result in activation of cathepsin D; as a consequence, kinins can be released, improving blood supply and leaving more cathepsin G available for the degradation of extracellular matrix.
Palavra-chave cathepsin D
fluorogenic substrates
Idioma Inglês
Data de publicação 2000-07-01
Publicado em Journal of Protein Chemistry. New York: Kluwer Academic/plenum Publ, v. 19, n. 5, p. 411-418, 2000.
ISSN 0277-8033 (Sherpa/Romeo, fator de impacto)
Publicador Kluwer Academic/plenum Publ
Extensão 411-418
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000165748000009
Endereço permanente

Exibir registro completo


Arquivo Tamanho Formato Visualização

Não existem arquivos associados a este item.

Este item está nas seguintes coleções



Minha conta