Effects of magnesium ions on recombinant human furin: selective activation of hydrolytic activity upon substrates derived from virus envelope glycoprotein

Effects of magnesium ions on recombinant human furin: selective activation of hydrolytic activity upon substrates derived from virus envelope glycoprotein

Author Izidoro, Mario A. Autor UNIFESP Google Scholar
Assis, Diego M. Autor UNIFESP Google Scholar
Oliveira, Vitor Autor UNIFESP Google Scholar
Santos, Jorge A. N. Autor UNIFESP Google Scholar
Juliano, Maria A. Autor UNIFESP Google Scholar
Lindberg, Iris Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Maryland
Abstract Here we report a detailed analysis of magnesium (Mg(2+)) ion effects on furin hydrolysis of fluorescent resonance energy transfer decapeptide substrates derived from canonical R-X-K/R-R furin cleavage motifs within certain viral envelope glycoproteins and eukaryotic proproteins. Using virus-derived sequences a selective activation of furin by Mg(2+) ions was observed as a result of cooperativity between furin subsites. Furin hydrolysis of the peptides Abz-SRRHKR down arrow FAGV-Q-EDDnp (from measles virus fusion protein F(o)) and Abz-RERRRKKR down arrow GLFG-Q-EDDnp (from Asian avian influenza A, H5N1) was activated between 60- and 80-fold by MgCl(2). It appears that virus envelope glycoprotein mutations have been selected to increase their susceptibility to furin within cells, a location where Mg(2+) is present in adequate concentrations for activation. Both the pH profile of furin and its intrinsic fluorescence were modified by Mg(2+) ions, which bind to furin with a K(d) value of 1.1 mM.
Keywords fluorescence
magnesium
peptidase
protease
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2010-09-01
Published in Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 391, n. 9, p. 1105-1112, 2010.
ISSN 1431-6730 (Sherpa/Romeo, impact factor)
Publisher Walter de Gruyter & Co
Extent 1105-1112
Origin http://dx.doi.org/10.1515/BC.2010.114
Access rights Closed access
Type Article
Web of Science ID WOS:000283654900010
URI http://repositorio.unifesp.br/handle/11600/32901

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