2os5

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File:2os5.jpg


2os5, resolution 1.60Å

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Macrophage migration inhibitory factor from Ancylostoma ceylanicum

OverviewOverview

Hookworms, parasitic nematodes that infect nearly one billion people, worldwide, are a major cause of anemia and malnutrition. We hypothesize, that hookworms actively manipulate the host immune response through the, production of specific molecules designed to facilitate infection by, larval stages and adult worm survival within the intestine. A full-length, cDNA encoding a secreted orthologue of the human cytokine, Macrophage, Migration Inhibitory Factor (MIF) has been cloned from the hookworm, Ancylostoma ceylanicum. Elucidation of the three-dimensional crystal, structure of recombinant AceMIF (rAceMIF) revealed an overall structural, homology with significant differences in the tautomerase sites of the, human and hookworm proteins. The relative bioactivities of human and, hookworm MIF proteins were compared using in vitro assays of tautomerase, activity, macrophage migration, and binding to MIF receptor CD74. The, activity of rAceMIF was not inhibited by the ligand ISO-1, which was, previously determined to be an inhibitor of the catalytic site of human, MIF. These data define unique immunological, structural, and functional, characteristics of AceMIF, thereby establishing the potential for, selectively inhibiting the hookworm cytokine as a means of reducing, parasite survival and disease pathogenesis.

About this StructureAbout this Structure

2OS5 is a Protein complex structure of sequences from Ancylostoma ceylanicum with as ligand. Known structural/functional Sites: , , and . Full crystallographic information is available from OCA.

ReferenceReference

Structural and functional characterization of a secreted hookworm Macrophage Migration Inhibitory Factor (MIF) that interacts with the human MIF receptor CD74., Cho Y, Jones BF, Vermeire JJ, Leng L, DiFedele L, Harrison LM, Xiong H, Kwong YK, Chen Y, Bucala R, Lolis E, Cappello M, J Biol Chem. 2007 Aug 10;282(32):23447-56. Epub 2007 Jun 13. PMID:17567581

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