Specificity of the dynorphin-processing endoprotease: Comparison with prohormone convertases

Specificity of the dynorphin-processing endoprotease: Comparison with prohormone convertases

Autor Berman, Y. Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Devi, L. A. Google Scholar
Instituição NYU
Universidade Federal de São Paulo (UNIFESP)
Resumo The cleavage specificity of a monobasic processing dynorphin converting endoprotease is examined with a series of quench fluorescent peptide substrates and compared with the cleavage specificity of prohormone convertases, A dynorphin B-29-derived peptide, Abz-Arg-Arg-Gln-Phe-Lys-Val-Val-Thr-Arg-Ser-Gln-eddnp (where Abz is o-aminobenzoyl and eddnp is ethylenediamine 2,4-dinitrophenyl), that contains both dibasic and monobasic cleavage sites is efficiently cleaved by the dynorphin converting enzyme and not cleaved by two propeptide processing enzymes, furin and prohormone convertase 1. A shorter prorenin-related peptide, Dnp-Arg-Met-Ala-Arg-Leu-Thr-Leu-eddnp, that contains a monobasic cleavage site is cleaved by the dynorphin converting enzyme and prohormone convertase 1 and not by furin. Substitution of the P1' position by Ala moderately affects cleavage by the dynorphin-processing enzyme and prohormone convertase 1. It is interesting that this substitution results in efficient cleavage by furin. the site of cleavage, as determined by matrix-assisted laser desorption/ionization time of flight mass spectrometry, is N-terminal to the Arg at the P1 position for the dynorphin converting enzyme and C-terminal to the Arg at the P1 position for furin and prohormone convertase 1. Peptides with additional basic residues at the P2 and at P4 positions also serve as substrates for the dynorphin converting enzyme, This enzyme cleaves shorter peptide substrates with significantly lower efficiency as compared with the longer peptide substrates, suggesting that the dynorphin converting enzyme prefers longer peptides that contain monobasic processing sites as substrates, Taken together, these results suggest that the cleavage specificity of the dynorphin converting enzyme is distinct but related to the cleavage specificity of the prohormone convertases and that multiple enzymes could be involved in the processing of peptide hormones and neuropeptides at monobasic and dibasic sites.
Palavra-chave dynorphins
enkephalin
posttranslational processing
prohormone convertases
furin
neuropeptide biosynthesis
Idioma Inglês
Data de publicação 1999-05-01
Publicado em Journal of Neurochemistry. Philadelphia: Lippincott Williams & Wilkins, v. 72, n. 5, p. 2120-2126, 1999.
ISSN 0022-3042 (Sherpa/Romeo, fator de impacto)
Publicador Lippincott Williams & Wilkins
Extensão 2120-2126
Fonte http://dx.doi.org/10.1046/j.1471-4159.1999.0722120.x
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000079753400040
Endereço permanente http://repositorio.unifesp.br/handle/11600/26068

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