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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Antigens, Differentiation, B-Lymphocyte / metabolism
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Antimalarials / chemistry
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Antimalarials / pharmacology
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Catalytic Domain
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Crystallography, X-Ray
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Histocompatibility Antigens Class II / metabolism
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Humans
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Intramolecular Oxidoreductases / chemistry
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Intramolecular Oxidoreductases / metabolism
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Macrophage Migration-Inhibitory Factors / antagonists & inhibitors*
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Macrophage Migration-Inhibitory Factors / chemistry*
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Macrophage Migration-Inhibitory Factors / metabolism
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Models, Molecular
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Protein Stability
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Protozoan Proteins / antagonists & inhibitors*
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Protozoan Proteins / chemistry*
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Protozoan Proteins / metabolism
Substances
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Antigens, Differentiation, B-Lymphocyte
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Antimalarials
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Histocompatibility Antigens Class II
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Macrophage Migration-Inhibitory Factors
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Protozoan Proteins
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invariant chain
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macrophage-migration inhibitory factor, Plasmodium falciparum
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Intramolecular Oxidoreductases
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MIF protein, human