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Crystallographic and receptor binding characterization of Plasmodium falciparum macrophage migration inhibitory factor complexed to two potent inhibitors.

ABSTRACT: We report the crystal structures of two inhibitors of Plasmodium falciparum macrophage migration inhibitory factor (PfMIF) with nanomolar Ki'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.

SUBMITTER: Pantouris G

PROVIDER: S-EPMC4207548 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Crystallographic and receptor binding characterization of Plasmodium falciparum macrophage migration inhibitory factor complexed to two potent inhibitors.

Pantouris Georgios G Rajasekaran Deepa D Baeza Garcia Alvaro A Ruiz Victor G VG Leng Lin L Jorgensen William L WL Bucala Richard R Lolis Elias J EJ

Journal of medicinal chemistry 20141008 20

We report the crystal structures of two inhibitors of Plasmodium falciparum macrophage migration inhibitory factor (PfMIF) with nanomolar Ki'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 Pf ...[more]

PMID: 25268646

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Characterization of a Plasmodium falciparum macrophage-migration inhibitory factor homologue.

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