Crystallographic and Receptor Binding Characterization of Plasmodium falciparum Macrophage Migration Inhibitory Factor Complexed to Two Potent Inhibitors

[Image: see text] We report the crystal structures of two inhibitors of Plasmodium falciparum macrophage migration inhibitory factor (PfMIF) with nanomolar K(i)’s, analyze their interactions with the active site of PfMIF, and provide explanations regarding their selectivity of PfMIF versus human MIF...

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Autores principales: Pantouris, Georgios, Rajasekaran, Deepa, Garcia, Alvaro Baeza, Ruiz, Victor G., Leng, Lin, Jorgensen, William L., Bucala, Richard, Lolis, Elias J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207548/
https://www.ncbi.nlm.nih.gov/pubmed/25268646
http://dx.doi.org/10.1021/jm501168q
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author Pantouris, Georgios
Rajasekaran, Deepa
Garcia, Alvaro Baeza
Ruiz, Victor G.
Leng, Lin
Jorgensen, William L.
Bucala, Richard
Lolis, Elias J.
author_facet Pantouris, Georgios
Rajasekaran, Deepa
Garcia, Alvaro Baeza
Ruiz, Victor G.
Leng, Lin
Jorgensen, William L.
Bucala, Richard
Lolis, Elias J.
author_sort Pantouris, Georgios
collection PubMed
description [Image: see text] We report the crystal structures of two inhibitors of Plasmodium falciparum macrophage migration inhibitory factor (PfMIF) with nanomolar K(i)’s, analyze their interactions with the active site of PfMIF, and provide explanations regarding their selectivity of PfMIF versus human MIF. These inhibitors were also found to selectively inhibit interactions between PfMIF and the human MIF receptor CD74. The results of this study provide the framework for the development of new therapeutics that target PfMIF.
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spelling pubmed-42075482015-09-30 Crystallographic and Receptor Binding Characterization of Plasmodium falciparum Macrophage Migration Inhibitory Factor Complexed to Two Potent Inhibitors Pantouris, Georgios Rajasekaran, Deepa Garcia, Alvaro Baeza Ruiz, Victor G. Leng, Lin Jorgensen, William L. Bucala, Richard Lolis, Elias J. J Med Chem [Image: see text] We report the crystal structures of two inhibitors of Plasmodium falciparum macrophage migration inhibitory factor (PfMIF) with nanomolar K(i)’s, analyze their interactions with the active site of PfMIF, and provide explanations regarding their selectivity of PfMIF versus human MIF. These inhibitors were also found to selectively inhibit interactions between PfMIF and the human MIF receptor CD74. The results of this study provide the framework for the development of new therapeutics that target PfMIF. American Chemical Society 2014-09-30 2014-10-23 /pmc/articles/PMC4207548/ /pubmed/25268646 http://dx.doi.org/10.1021/jm501168q Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
spellingShingle Pantouris, Georgios
Rajasekaran, Deepa
Garcia, Alvaro Baeza
Ruiz, Victor G.
Leng, Lin
Jorgensen, William L.
Bucala, Richard
Lolis, Elias J.
Crystallographic and Receptor Binding Characterization of Plasmodium falciparum Macrophage Migration Inhibitory Factor Complexed to Two Potent Inhibitors
title Crystallographic and Receptor Binding Characterization of Plasmodium falciparum Macrophage Migration Inhibitory Factor Complexed to Two Potent Inhibitors
title_full Crystallographic and Receptor Binding Characterization of Plasmodium falciparum Macrophage Migration Inhibitory Factor Complexed to Two Potent Inhibitors
title_fullStr Crystallographic and Receptor Binding Characterization of Plasmodium falciparum Macrophage Migration Inhibitory Factor Complexed to Two Potent Inhibitors
title_full_unstemmed Crystallographic and Receptor Binding Characterization of Plasmodium falciparum Macrophage Migration Inhibitory Factor Complexed to Two Potent Inhibitors
title_short Crystallographic and Receptor Binding Characterization of Plasmodium falciparum Macrophage Migration Inhibitory Factor Complexed to Two Potent Inhibitors
title_sort crystallographic and receptor binding characterization of plasmodium falciparum macrophage migration inhibitory factor complexed to two potent inhibitors
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207548/
https://www.ncbi.nlm.nih.gov/pubmed/25268646
http://dx.doi.org/10.1021/jm501168q
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