ATP effects on insulin-degrading enzyme are mediated primarily through its triphosphate moiety

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dc.contributor.author Song, E. S.
dc.contributor.author Juliano, Maria Aparecida [UNIFESP]
dc.contributor.author Juliano, Luiz [UNIFESP]
dc.contributor.author Fried, M. G.
dc.contributor.author Wagner, S. L.
dc.contributor.author Hersh, L. B.
dc.date.accessioned 2016-01-24T12:37:32Z
dc.date.available 2016-01-24T12:37:32Z
dc.date.issued 2004-12-24
dc.identifier http://dx.doi.org/10.1074/jbc.M411177200
dc.identifier.citation Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 279, n. 52, p. 54216-54220, 2004.
dc.identifier.issn 0021-9258
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/28053
dc.description.abstract It has been reported previously that ATP inhibits the insulysin reaction (Camberos, M. C., Perez, A. A., Udrisar, D. P., Wanderley, M. I., and Cresto, J. C. ( 2001) Exp. Biol. Med. 226, 334-341). We report here that with 2-aminobenzoyl-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl as substrate, ATP and other nucleotides increase the rate >20-fold in Tris buffer. There is no specificity with respect to the nucleotide; however, ATP is more effective than ADP, which is more effective than AMP. Triphosphate itself was as effective as ATP, indicating it is this moiety that is responsible for activation. the binding of triphosphate was shown to be at a site distinct from the active site, thus acting as a noncompetitive activator. With the physiological substrates insulin and amyloid beta peptide, nucleotides and triphosphate were without effect. However, with small physiological peptides such as bradykinin and dynorphin B-9, ATP and triphosphate increased the rate of hydrolysis similar to10-fold. Triphosphate and ATP shifted the oligomeric state of the enzyme from primarily dimer-tetramers to a monomer. These data suggest the presence of an allosteric regulatory site on insulysin that may shift its specificity toward small peptide substrates. en
dc.format.extent 54216-54220
dc.language.iso eng
dc.publisher Amer Soc Biochemistry Molecular Biology Inc
dc.relation.ispartof Journal of Biological Chemistry
dc.rights Acesso aberto
dc.title ATP effects on insulin-degrading enzyme are mediated primarily through its triphosphate moiety en
dc.type Artigo
dc.contributor.institution Univ Kentucky
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Neurogenet Inc
dc.description.affiliation Univ Kentucky, Coll Med, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA
dc.description.affiliation Escola Paulista Med, Dept Biophys, BR-04023900 São Paulo, Brazil
dc.description.affiliation Neurogenet Inc, La Jolla, CA 92037 USA
dc.description.affiliationUnifesp Escola Paulista Med, Dept Biophys, BR-04023900 São Paulo, Brazil
dc.identifier.doi 10.1074/jbc.M411177200
dc.description.source Web of Science
dc.identifier.wos WOS:000225793600041



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