Repository logo
 
Publication

Rationalizing the decavanadate(V) and oxidovanadium(IV) binding to G-Actin and the competition with decaniobate(V) and ATP

2021-01Journal article Restricted access
Simple item page
dc.contributor.authorGiuseppe, Sciortino
dc.contributor.authorAureliano, M.
dc.contributor.authorEugenio, Garribba
dc.date.accessioned2021-02-10T08:54:03Z
dc.date.available2022-01-04T01:30:14Z
dc.date.issued2021-01
dc.description.abstractThe experimental data collected over the past 15 years on the interaction of decavanadate(V) (V10O286-; V10), a polyoxometalate (POM) with promising anticancer and antibacterial action, with G-actin, were rationalized by using several computational approaches (docking, density functional theory (DFT), and molecular dynamics (MD)). Moreover, a comparison with the isostructural and more stable decaniobate(V) (Nb10O286-; Nb10) was carried out. Four binding sites were identified, named α, β, γ, and δ, the site α being the catalytic nucleotide site located in the cleft of the enzyme at the interface of the subdomains II and IV. It was observed that the site α is preferred by V10, whereas Nb10 is more stable at the site β; this indicates that, differently from other proteins, G-actin could contemporaneously bind the two POMs, whose action would be synergistic. Both decavanadate and decaniobate induce conformational rearrangements in G-actin, larger for V10 than Nb10. Moreover, the binding mode of oxidovanadium(IV) ion, VIVO2+, formed upon the reduction of decavanadate(V) by the -SH groups of accessible cysteine residues, is also found in the catalytic site α with (His161, Asp154) coordination; this adduct overlaps significantly with the region where ATP is bound, accounting for the competition between V10 and its reduction product VIVO2+ with ATP, as previously observed by EPR spectroscopy. Finally, the competition with ATP was rationalized: since decavanadate prefers the nucleotide site α, Ca2+-ATP displaces V10 from this site, while the competition is less important for Nb10 because this POM shows a higher affinity for β than for site α. A relevant consequence of this paper is that other metallodrug-protein systems, in the absence or presence of eventual inhibitors and/or competition with molecules of the organism, could be studied with the same approach, suggesting important elements for an explanation of the biological data and a rational drug design.pt_PT
dc.description.sponsorshipPortuguese Foundation for Science and Technology UIDB/04326/2020pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationSciortino et al, Inorg. Chem 60 (20211pt_PT
dc.identifier.doi10.1021/acs.inorgchem.0c02971pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.1/15068
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Chemical Societypt_PT
dc.subjectDecavanadatept_PT
dc.subjectActinpt_PT
dc.subjectDecaniobatept_PT
dc.subjectMolecular dockingpt_PT
dc.titleRationalizing the decavanadate(V) and oxidovanadium(IV) binding to G-Actin and the competition with decaniobate(V) and ATPpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage344pt_PT
oaire.citation.startPage334pt_PT
oaire.citation.titleInorganic Chemistrypt_PT
oaire.citation.volume60pt_PT
person.familyNameAureliano
person.givenNameManuel
person.identifier584146
person.identifier.ciencia-idAA14-3490-DC5E
person.identifier.orcid0000-0003-4858-3201
person.identifier.ridI-3283-2012
person.identifier.scopus-author-id6603412860
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationbb413661-7edd-4b57-8338-33889cfd05db
relation.isAuthorOfPublication.latestForDiscoverybb413661-7edd-4b57-8338-33889cfd05db

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Sciortinoetal_2021_InorChem.pdf
Size:
4.74 MB
Format:
Adobe Portable Document Format
Download

Collections

FCT2-Artigos (em revistas ou actas indexadas)