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dc.creatorVujačić Nikezić, Ana V.
dc.creatorJanjić, Goran V.
dc.creatorBondžić, Aleksandra
dc.creatorZarić, Božidarka
dc.creatorVasić Anićijević, Dragana D.
dc.creatorMomić, Tatjana
dc.creatorVasić, Vesna M.
dc.date.accessioned2018-09-14T12:13:57Z
dc.date.available2018-09-14T12:13:57Z
dc.date.issued2018
dc.identifier.issn1756-5901 (print)
dc.identifier.issn1756-591X (electronic)
dc.identifier.urihttp://xlink.rsc.org/?DOI=C8MT00111A
dc.identifier.urihttp://vinar.vin.bg.ac.rs/handle/123456789/7812
dc.description.abstractThe present paper deals with investigation of the interaction between selected simple structure Au(iii) ([AuCl4]-, [AuCl2(dmso)2]+, [AuCl2(bipy)]+) and Pt(ii) ([PtCl2(dmso)2]) complexes with Na/K-ATPase as the target enzyme, using an experimental and theoretical approach. Reaction stoichiometries and binding constants for these enzyme/complex systems were determined, while kinetic measurements were used in order to reveal the type of inhibition. Based on the results obtained by quantum mechanical calculations (electrostatic surface potential (ESP), volume and surface of the complexes) the nature of the investigated complexes was characterized. By using the solvent accessible surface area (SASA) applied on specific inhibitory sites (ion channel and intracellular domains) the nature of these sites was described. Docking studies were used to determine the theoretical probability of the non-covalent metal binding site positions. Inhibition studies implied that all the investigated complexes decreased the activity of the enzyme while the kinetic analysis indicated an uncompetitive mode of inhibition for the selected complexes. Docking results suggested that the main inhibitory site of all these complexes is located in the ion translocation pathway on the extracellular side in the E2P enzyme conformation, similar to the case of cardiac glycosides, specific Na/K-ATPase inhibitors. Also, based on our knowledge, the hydrolyzed forms of [AuCl4]- and [PtCl2(dmso)2] complexes were investigated for the first time by theoretical calculations in this paper. Thereby, a new inhibitory site situated between the M2 and M4 helices was revealed. Binding in this site induces conformational changes in the enzyme domains and perturbs the E1-E2P conformational equilibrium, causing enzyme inhibition.en
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172023/RS//
dc.rightsrestrictedAccess
dc.sourceMetallomics
dc.titleInteraction of Au(iii) and Pt(ii) complexes with Na/K-ATPase: experimental and theoretical study of reaction stoichiometry and binding sitesen
dc.typearticleen
dc.rights.licenseARR
dcterms.abstractВасић, Весна М.; Јањић, Горан В.; Вујачић Никезић, Aна В.; Бонджић, Aлександра М.; Зарић, Божидарка Л.; Васић-Aнићијевић, Драгана Д.; Момић, Татјана Г.;
dc.rights.holder© The Royal Society of Chemistry
dc.citation.volume10
dc.citation.issue7
dc.citation.spage1003
dc.citation.epage1015
dc.identifier.wos000439583800011
dc.identifier.doi10.1039/C8MT00111A
dc.identifier.pmid29978878
dc.type.versionpublishedVersion
dc.identifier.scopus2-s2.0-85050547953


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