DETERMINANTS OF THE UNUSUAL CLEAVAGE SPECIFICITY OF LYSYL-BRADYKININ-RELEASING KALLIKREINS

DETERMINANTS OF THE UNUSUAL CLEAVAGE SPECIFICITY OF LYSYL-BRADYKININ-RELEASING KALLIKREINS

Author Chagas, Jair Ribeiro Autor UNIFESP Google Scholar
Portaro, Fernanda Calheta Vieira Autor UNIFESP Google Scholar
Hirata, Izaura Yoshico Autor UNIFESP Google Scholar
Almeida, Paulo Cezar de Autor UNIFESP Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Prado, Eline Sant'Anna Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Kinetic data for the hydrolysis by human tissue kallikrein of fluorogenic peptides with o-aminobenzoyl-Phe-Arg (Abz-FR) as the acyl group and different leaving groups demonstrate that interactions with the S'(1), S'(2), and S'(3), subsites are important for cleavage efficiency. In addition, studies on the hydrolysis of fluorogenic peptides with the human kininogen sequence spanning the scissile Met-Lys bond [Abz-M-I-S-L-M-K-R-P-N-(2,4-dinitrophenyl)ethylenediamine] and analogues with different residues at positions P'(1), P'(2) and P'(3) showed that (a) the presence of a proline residue at P'(3) and the interactions with the tissue kallikrein-binding sites S-2 to S'(2) are determinants of Met-Lys bond cleavage and (b) residues P-3, P-4 and/or P-5 are important for cleavage efficiency. The substitution of phenylalanine for methionine or arginine in substrates with scissile Met-Lys or Arg-Xaa bonds demonstrated that lysyl-bradykinin-releasing tissue kallikreins also have a primary specificity for phenylalanine. The replacement of arginine by phenylalanine in (D)P-F-R-p-nitroanilide (pNA) produced an efficient and specific chromogenic substrate, (D)P-F-F-pNA, for the lysyl-bradykinin-releasing tissue kallikreins as it is resistant to plasma kallikrein and other arginine hydrolases.
Language English
Date 1995-02-15
Published in Biochemical Journal. London: Portland Press, v. 309, n. 1, p. 63-69, 1995.
ISSN 0264-6021 (Sherpa/Romeo, impact factor)
Publisher Portland Press
Extent 63-69
Origin http://dx.doi.org/10.1042/bj3060063
Access rights Open access Open Access
Type Article
Web of Science ID WOS:A1995QH16600010
URI http://repositorio.unifesp.br/11600/42796

Show full item record




File

File Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Search


Browse

Statistics

My Account