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Crystallographic and Receptor Binding Characterization of Plasmodium falciparum Macrophage Migration Inhibitory Factor Complexed to Two Potent Inhibitors
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...
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| Published in: | Journal of medicinal chemistry 2014-10, Vol.57 (20), p.8652-8656 |
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| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
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| cites | cdi_FETCH-LOGICAL-a438t-9b996316ffa5c0f8c99f55d665f6f33feff0a219424dbd222bf8bd7fc10c331d3 |
| container_end_page | 8656 |
| container_issue | 20 |
| container_start_page | 8652 |
| container_title | Journal of medicinal chemistry |
| container_volume | 57 |
| creator | Pantouris, Georgios Rajasekaran, Deepa Baeza Garcia, Alvaro Ruiz, Victor G. Leng, Lin Jorgensen, William L. Bucala, Richard Lolis, Elias J. |
| description | 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. |
| doi_str_mv | 10.1021/jm501168q |
| format | article |
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These inhibitors were also found to selectively inhibit interactions between PfMIF and the human MIF receptor CD74. 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Med. Chem</addtitle><description>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.</description><subject>Antigens, Differentiation, B-Lymphocyte - metabolism</subject><subject>Antimalarials - chemistry</subject><subject>Antimalarials - pharmacology</subject><subject>Brief</subject><subject>Catalytic Domain</subject><subject>Crystallography, X-Ray</subject><subject>Histocompatibility Antigens Class II - metabolism</subject><subject>Humans</subject><subject>Intramolecular Oxidoreductases - chemistry</subject><subject>Intramolecular Oxidoreductases - metabolism</subject><subject>Macrophage Migration-Inhibitory Factors - antagonists & inhibitors</subject><subject>Macrophage Migration-Inhibitory Factors - chemistry</subject><subject>Macrophage Migration-Inhibitory Factors - metabolism</subject><subject>Models, Molecular</subject><subject>Plasmodium falciparum</subject><subject>Protein Stability</subject><subject>Protozoan Proteins - antagonists & inhibitors</subject><subject>Protozoan Proteins - chemistry</subject><subject>Protozoan Proteins - metabolism</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNqFkU1v1DAQhi0EokvhwB9AviDBIeCveJMLUolaqNSKCpWzNfHHxqskTu0EuvwT_i2GLQtISJxmpHn0aGZehJ5S8ooSRl9vh5JQKqube2hFS0YKURFxH60IYaxgkvEj9CilLSGEU8YfoiNWMllJIVfoWxN3aYa-D5sIU-c1htHgj1bbaQ4Rv_Wj8eMGNx1E0LON_ivMPow4OHzVQxqC8cuAHfTaTxBzewk6hqmDjcWXPjt_0udj51ufhTt8ljVZ3IRh6u2tNXgO-PpLwFdhtuP8m0yP0YOsTfbJXT1Gn85Or5v3xcWHd-fNyUUBgldzUbd1LTmVzkGpiat0XbuyNFKWTjrOnXWOAKO1YMK0hjHWuqo1a6cp0ZxTw4_Rm713WtrBGp23iNCrKfoB4k4F8Orvyeg7tQmflWBkXYoqC17cCWK4WWya1eCTtn0Pow1LUnTN1rISNeX_RyWVIsOcZfTlHs3vTClad9iIEvUjdXVIPbPP_jzhQP6KOQPP9wDopLZhiWP-6D9E3wG14rjc</recordid><startdate>20141023</startdate><enddate>20141023</enddate><creator>Pantouris, Georgios</creator><creator>Rajasekaran, Deepa</creator><creator>Baeza Garcia, Alvaro</creator><creator>Ruiz, Victor G.</creator><creator>Leng, Lin</creator><creator>Jorgensen, William L.</creator><creator>Bucala, Richard</creator><creator>Lolis, Elias J.</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>M7N</scope><scope>5PM</scope></search><sort><creationdate>20141023</creationdate><title>Crystallographic and Receptor Binding Characterization of Plasmodium falciparum Macrophage Migration Inhibitory Factor Complexed to Two Potent Inhibitors</title><author>Pantouris, Georgios ; 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Med. Chem</addtitle><date>2014-10-23</date><risdate>2014</risdate><volume>57</volume><issue>20</issue><spage>8652</spage><epage>8656</epage><pages>8652-8656</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>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.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>25268646</pmid><doi>10.1021/jm501168q</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of medicinal chemistry, 2014-10, Vol.57 (20), p.8652-8656 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4207548 |
| source | American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list) |
| subjects | Antigens, Differentiation, B-Lymphocyte - metabolism Antimalarials - chemistry Antimalarials - pharmacology Brief Catalytic Domain Crystallography, X-Ray Histocompatibility Antigens Class II - metabolism Humans Intramolecular Oxidoreductases - chemistry Intramolecular Oxidoreductases - metabolism Macrophage Migration-Inhibitory Factors - antagonists & inhibitors Macrophage Migration-Inhibitory Factors - chemistry Macrophage Migration-Inhibitory Factors - metabolism Models, Molecular Plasmodium falciparum Protein Stability Protozoan Proteins - antagonists & inhibitors Protozoan Proteins - chemistry Protozoan Proteins - metabolism |
| title | Crystallographic and Receptor Binding Characterization of Plasmodium falciparum Macrophage Migration Inhibitory Factor Complexed to Two Potent Inhibitors |
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