Crystallographic and Receptor Binding Characterization of Plasmodium falciparum Macrophage Migration Inhibitory Factor Complexed to Two Potent Inhibitors
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- 作者：Georgios Pantouris ; Deepa Rajasekaran ; Alvaro Baeza Garcia ; Victor G. Ruiz ; Lin Leng ; William L. Jorgensen ; Richard Bucala ; Elias J. Lolis
- 刊名：Journal of Medicinal Chemistry
- 出版年：2014
- 出版时间：October 23, 2014
- 年：2014
- 卷：57
- 期：20
- 页码：8652-8656
- 全文大小：276K
- ISSN：1520-4804
文摘
We report the crystal structures of two inhibitors of Plasmodium falciparum macrophage migration inhibitory factor (PfMIF) with nanomolar Ki鈥檚, 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.