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

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dc.contributor.author Pimenta, D. C.
dc.contributor.author Chen, V. C.
dc.contributor.author Chao, J.
dc.contributor.author Juliano, M. A.
dc.contributor.author Juliano, L.
dc.date.accessioned 2016-01-24T12:31:07Z
dc.date.available 2016-01-24T12:31:07Z
dc.date.issued 2000-07-01
dc.identifier http://dx.doi.org/10.1023/A:1026432402259
dc.identifier.citation Journal of Protein Chemistry. New York: Kluwer Academic/plenum Publ, v. 19, n. 5, p. 411-418, 2000.
dc.identifier.issn 0277-8033
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/26340
dc.description.abstract 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. en
dc.format.extent 411-418
dc.language.iso eng
dc.publisher Kluwer Academic/plenum Publ
dc.relation.ispartof Journal of Protein Chemistry
dc.rights Acesso restrito
dc.subject cathepsin D en
dc.subject kallistatin en
dc.subject antichymotrypsin en
dc.subject serpin en
dc.subject fluorogenic substrates en
dc.title alpha(1)-antichymotrypsin and kallistatin hydrolysis by human cathepsin D en
dc.type Artigo
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Med Univ S Carolina
dc.description.affiliation UNIFESP, Escola Paulista Med, Dept Biofis, BR-04044020 São Paulo, Brazil
dc.description.affiliation Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA
dc.description.affiliationUnifesp UNIFESP, Escola Paulista Med, Dept Biofis, BR-04044020 São Paulo, Brazil
dc.identifier.doi 10.1023/A:1026432402259
dc.description.source Web of Science
dc.identifier.wos WOS:000165748000009



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