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In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites

ATP2, a putative type 4 P-type ATPase, is a phosphatidylinositol-4-phosphate (PI4P)-regulated phospholipid transporter with an interesting potential as an antimalarial drug target due to its conservation across Plasmodium species and its essential role in the life cycle of Plasmodium falciparum. Des...

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Autores principales: López-Martín, Mario, Renault, Pedro, Giraldo, Jesus, Vázquez-Ibar, José Luis, Perálvarez-Marín, Alex
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325222/
https://www.ncbi.nlm.nih.gov/pubmed/35877905
http://dx.doi.org/10.3390/membranes12070702
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author López-Martín, Mario
Renault, Pedro
Giraldo, Jesus
Vázquez-Ibar, José Luis
Perálvarez-Marín, Alex
author_facet López-Martín, Mario
Renault, Pedro
Giraldo, Jesus
Vázquez-Ibar, José Luis
Perálvarez-Marín, Alex
author_sort López-Martín, Mario
collection PubMed
description ATP2, a putative type 4 P-type ATPase, is a phosphatidylinositol-4-phosphate (PI4P)-regulated phospholipid transporter with an interesting potential as an antimalarial drug target due to its conservation across Plasmodium species and its essential role in the life cycle of Plasmodium falciparum. Despite its importance, the exact mechanism of its action and regulation is still not fully understood. In this study we used coarse-grained molecular dynamics (CG-MD) to elucidate the lipid–protein interactions between a heterogeneous lipid membrane containing phosphatidylinositol and Plasmodium chabaudi ATP2 (PcATP2), an ortholog of P. falciparum ATP2. Our study reveals structural information of the lipid fingerprint of ATP2, and provides structural information on the potential phosphatidylinositol allosteric binding site. Moreover, we identified a set of evolutionary conserved residues that may play a key role in the binding and stabilization of lipids in the binding pocket.
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spelling pubmed-93252222022-07-27 In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites López-Martín, Mario Renault, Pedro Giraldo, Jesus Vázquez-Ibar, José Luis Perálvarez-Marín, Alex Membranes (Basel) Article ATP2, a putative type 4 P-type ATPase, is a phosphatidylinositol-4-phosphate (PI4P)-regulated phospholipid transporter with an interesting potential as an antimalarial drug target due to its conservation across Plasmodium species and its essential role in the life cycle of Plasmodium falciparum. Despite its importance, the exact mechanism of its action and regulation is still not fully understood. In this study we used coarse-grained molecular dynamics (CG-MD) to elucidate the lipid–protein interactions between a heterogeneous lipid membrane containing phosphatidylinositol and Plasmodium chabaudi ATP2 (PcATP2), an ortholog of P. falciparum ATP2. Our study reveals structural information of the lipid fingerprint of ATP2, and provides structural information on the potential phosphatidylinositol allosteric binding site. Moreover, we identified a set of evolutionary conserved residues that may play a key role in the binding and stabilization of lipids in the binding pocket. MDPI 2022-07-12 /pmc/articles/PMC9325222/ /pubmed/35877905 http://dx.doi.org/10.3390/membranes12070702 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
López-Martín, Mario
Renault, Pedro
Giraldo, Jesus
Vázquez-Ibar, José Luis
Perálvarez-Marín, Alex
In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites
title In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites
title_full In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites
title_fullStr In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites
title_full_unstemmed In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites
title_short In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the Essential P4-ATPase of Malaria Parasites
title_sort in silico assessment of the lipid fingerprint signature of atp2, the essential p4-atpase of malaria parasites
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325222/
https://www.ncbi.nlm.nih.gov/pubmed/35877905
http://dx.doi.org/10.3390/membranes12070702
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