Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/4914
DC FieldValueLanguage
dc.contributor.authorA., Conaen_us
dc.contributor.authorManetti, Fabrizioen_us
dc.contributor.authorR., Leoneen_us
dc.contributor.authorCorelli, Federicoen_us
dc.contributor.authorP., Tavladorakien_us
dc.contributor.authorF., Polticellien_us
dc.contributor.authorBotta, Maurizioen_us
dc.date.accessioned2021-03-30T15:45:30Z-
dc.date.available2021-03-30T15:45:30Z-
dc.date.issued2004-
dc.identifier.issn0006-2960en_US
dc.identifier.urihttp://hdl.handle.net/20.500.12779/4914-
dc.description36844en_US
dc.description.abstractMaize polyamine oxidase (MPAO), the only member of the polyamine oxidase (PAO) family whose three-dimensional structure is known, is characterized by a 30 Å long U-shaped catalytic tunnel located between the substrate binding domain and the FAD. To shed light on the MPAO ligand binding mode, we studied the inhibition properties of linear diamines, agmatine, prenylagmatine (G3), G3 analogues, and guazatine, and analyzed the structural determinants of their biological activity. Linear diamines competitively inhibited MPAO, with the inhibitory activity increasing as a function of the number of methylene groups. With regard to the guanidino competitive inhibitors, including agmatine, G3, and G3 analogues, the presence of a hydrophobic substituent constitutes the principal factor influencing MPAO inhibition, as the addition of a hydrophobic substituent to the guanidino group of both G3 and G3 analogues greatly increases the inhibitory activity. Moreover, results obtained by a molecular modeling procedure indicated that in their preferred orientation, G3 analogues point the ammonium group toward the narrow entrance of the tunnel, while the terminal hydrophobic group is located within the large entrance. The high binding affinity for MPAO exhibited by G3 and G3 analogues bearing a prenyl group as a substituent on the guanidino moiety is in agreement with the observation that the prenyl group binds in a well-defined hydrophobic pocket, mainly formed by aromatic residues. Finally, docking simulations performed with the charged and uncharged forms of MPAO inhibitors indicate that the stereoelectronic properties of the MPAO active site are consistent with the binding of inhibitors in the protonated form.en_US
dc.language.isoenen_US
dc.relationNoneen_US
dc.relation.ispartofBIOCHEMISTRYen_US
dc.titleMolecular Basis for the Binding of Competitive Inhibitors of Maize Polyamine Oxidaseen_US
dc.typeArticleen_US
dc.identifier.doi10.1021/bi036152zen_US
dc.identifier.pmid15035614en_US
dc.identifier.scopus2-s2.0-1642309250en_US
dc.identifier.isiWOS:000220443500014en_US
dc.relation.volume43en_US
dc.relation.issue12en_US
dc.description.firstpage3426en_US
dc.description.lastpage3435en_US
dc.description.thirdmissionNot applicableen_US
item.cerifentitytypePublications-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypeArticle-
item.fulltextNo Fulltext-
crisitem.author.orcid0000-0002-9598-2339-
crisitem.author.orcid0000-0002-5750-4504-
crisitem.author.orcid0000-0003-0456-6995-
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