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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Detalles Bibliográficos
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
Descripción
Sumario:[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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