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A computational assessment of the predicted structures of Human Macrophage Migration Inhibitory Factor 1 orthologs in parasites and its affinity to human CD74 receptor

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dc.contributor.author Machicado, C.
dc.contributor.author Marcos, L. A.
dc.date.accessioned 2019-01-25T16:36:28Z
dc.date.available 2019-01-25T16:36:28Z
dc.date.issued 2017
dc.identifier.uri https://hdl.handle.net/20.500.12866/4842
dc.description.abstract The human macrophage migration inhibitory factor 1 (Hu-MIF-1) is a protein involved in the inflammatory and immunology response to parasite infection. In the present study, the existence of Hu-MIF-1 from parasites have been explored by mining WormBase. A total of 35 helminths were found to have Hu-MIF-1 homologs, including some parasites of importance for public health. Physicochemical, structural, and biological properties of Hu-MIF-1 were compared with its orthologs in parasites showing that most of these are secretory proteins, with positive net charge and presence of the Cys-Xaa-Xaa-Cys motif that is critical for its oxidoreductase activity. The inhibitor-binding site present in Hu-MIF-1 is well conserved among parasite MIFs suggesting that Hu-MIF inhibitors may target orthologs in pathogens. The binding of Hu-MIF-1 to its cognate receptor CD74 was predicted by computer-assisted docking, and it resulted to be very similar to the predicted complexes formed by parasite MIFs and human CD74. More than 1 plausible conformation of MIFs in the extracellular loops of CD74 may be possible as demonstrated by the different predicted conformations of MIF orthologs in complex with CD74. Parasite MIFs in complex with CD74 resulted with some charged residues oriented to CD74, which was not observed in the Hu-MIF-1/CD74 complex. Our findings predict the binding mode of Hu-MIF-1 and orthologs with CD74, which can assist in the design of novel MIF inhibitors. Whether the parasite MIFs function specifically subvert host immune responses to suit the parasite is an open question that needs to be further investigated. Future research should lead to a better understanding of parasite MIF action in the parasite biology. en_US
dc.language.iso eng
dc.publisher Wiley
dc.relation.ispartof urn:issn:1099-1352
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Biophysics en_US
dc.subject Biochemistry & Molecular Biology en_US
dc.subject plasmodium-falciparum en_US
dc.subject crystal-structure en_US
dc.subject 3-dimensional structures en_US
dc.subject CD74 en_US
dc.subject cytokine en_US
dc.subject electrostatic potential en_US
dc.subject factor mif en_US
dc.subject giardia-lamblia en_US
dc.subject homology modelling en_US
dc.subject host macrophages en_US
dc.subject macrophage en_US
dc.subject migration-Inhibitory Factor en_US
dc.subject molecular docking en_US
dc.subject oligomerization state en_US
dc.subject sequence alignment en_US
dc.subject trichomonas-vaginalis en_US
dc.title A computational assessment of the predicted structures of Human Macrophage Migration Inhibitory Factor 1 orthologs in parasites and its affinity to human CD74 receptor en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1002/jmr.2640
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.03

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