Inhibition of trypanosomal cysteine proteinases by their propeptides

Inhibition of trypanosomal cysteine proteinases by their propeptides

Autor Lalmanach, G. Google Scholar
Lecaille, F. Google Scholar
Chagas, Jair Ribeiro Autor UNIFESP Google Scholar
Authie, E. Google Scholar
Scharfstein, J. Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Gauthier, F. Google Scholar
Instituição Univ Tours
Universidade Federal de São Paulo (UNIFESP)
Int Livestock Res Inst
Universidade Federal do Rio de Janeiro (UFRJ)
Resumo The ability of the prodomains of trypanosomal cysteine proteinases to inhibit their active form was studied using a set of 23 overlapping 15-mer peptides covering the whole prosequence of congopain, the major cysteine proteinase of Trypanosoma congolense. Three consecutive peptides with a common 5-mer sequence YHNGA were competitive inhibitors of congopain. A shorter synthetic peptide consisting of this 5-mer sequence flanked by two Ala residues (AYHNGAA) also inhibited purified congopain. No residue critical for inhibition was identified in this sequence, but a significant improvement in K-i value was obtained upon N-terminal elongation. Procongopain-derived peptides did not inhibit lysosomal cathepsins B and L but did inhibit native cruzipain (from Dm28c clone epimastigotes), the major cysteine proteinase of Trypanosoma cruzi, the proregion of which also contains the sequence YHNGA. the positioning of the YHNGA inhibitory sequence within the prosegment of trypanosomal proteinases is similar to that covering the active site in the prosegment of cysteine proteinases, the three-dimensional structure of which has been resolved. This strongly suggests that trypanosomal proteinases, despite their long C-terminal extension, have a prosegment that folds similarly to that in related mammal and plant cysteine proteinases, resulting in reverse binding within the active site, Such reverse binding could also occur for short procongopain-derived inhibitory peptides, based on their resistance to proteolysis and their ability to retain inhibitory activity after prolonged incubation. in contrast, homologous peptides in related cysteine proteinases did not inhibit trypanosomal proteinases and were rapidly cleaved by these enzymes.
Idioma Inglês
Data de publicação 1998-09-25
Publicado em Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 273, n. 39, p. 25112-25116, 1998.
ISSN 0021-9258 (Sherpa/Romeo, fator de impacto)
Publicador Amer Soc Biochemistry Molecular Biology Inc
Extensão 25112-25116
Fonte http://dx.doi.org/10.1074/jbc.273.39.25112
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000076085400019
Endereço permanente http://repositorio.unifesp.br/handle/11600/25960

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