Interaction of Au(iii) and Pt(ii) complexes with Na/K-ATPase: experimental and theoretical study of reaction stoichiometry and binding sites
Authorized Users Only
2018
Authors
Vujačić Nikezić, Ana V.Janjić, Goran V.
Bondžić, Aleksandra M.
Zarić, Božidarka
Vasić Anićijević, Dragana D.
Momić, Tatjana
Vasić, Vesna M.
Article (Published version)
,
© The Royal Society of Chemistry
Metadata
Show full item recordAbstract
The 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 complexe...s 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.
Source:
Metallomics, 2018, 10, 7, 1003-1015Funding / projects:
DOI: 10.1039/C8MT00111A
ISSN: 1756-5901; 1756-591X
PubMed: 29978878
WoS: 000439583800011
Scopus: 2-s2.0-85050547953
Collections
Institution/Community
VinčaTY - JOUR AU - Vujačić Nikezić, Ana V. AU - Janjić, Goran V. AU - Bondžić, Aleksandra M. AU - Zarić, Božidarka AU - Vasić Anićijević, Dragana D. AU - Momić, Tatjana AU - Vasić, Vesna M. PY - 2018 UR - http://xlink.rsc.org/?DOI=C8MT00111A UR - https://vinar.vin.bg.ac.rs/handle/123456789/7812 AB - The 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. T2 - Metallomics T1 - Interaction of Au(iii) and Pt(ii) complexes with Na/K-ATPase: experimental and theoretical study of reaction stoichiometry and binding sites VL - 10 IS - 7 SP - 1003 EP - 1015 DO - 10.1039/C8MT00111A ER -
@article{ author = "Vujačić Nikezić, Ana V. and Janjić, Goran V. and Bondžić, Aleksandra M. and Zarić, Božidarka and Vasić Anićijević, Dragana D. and Momić, Tatjana and Vasić, Vesna M.", year = "2018", abstract = "The 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.", journal = "Metallomics", title = "Interaction of Au(iii) and Pt(ii) complexes with Na/K-ATPase: experimental and theoretical study of reaction stoichiometry and binding sites", volume = "10", number = "7", pages = "1003-1015", doi = "10.1039/C8MT00111A" }
Vujačić Nikezić, A. V., Janjić, G. V., Bondžić, A. M., Zarić, B., Vasić Anićijević, D. D., Momić, T.,& Vasić, V. M.. (2018). Interaction of Au(iii) and Pt(ii) complexes with Na/K-ATPase: experimental and theoretical study of reaction stoichiometry and binding sites. in Metallomics, 10(7), 1003-1015. https://doi.org/10.1039/C8MT00111A
Vujačić Nikezić AV, Janjić GV, Bondžić AM, Zarić B, Vasić Anićijević DD, Momić T, Vasić VM. Interaction of Au(iii) and Pt(ii) complexes with Na/K-ATPase: experimental and theoretical study of reaction stoichiometry and binding sites. in Metallomics. 2018;10(7):1003-1015. doi:10.1039/C8MT00111A .
Vujačić Nikezić, Ana V., Janjić, Goran V., Bondžić, Aleksandra M., Zarić, Božidarka, Vasić Anićijević, Dragana D., Momić, Tatjana, Vasić, Vesna M., "Interaction of Au(iii) and Pt(ii) complexes with Na/K-ATPase: experimental and theoretical study of reaction stoichiometry and binding sites" in Metallomics, 10, no. 7 (2018):1003-1015, https://doi.org/10.1039/C8MT00111A . .