3gyu

Nuclear receptor DAF-12 from parasitic nematode Strongyloides stercoralis in complex with its physiological ligand dafachronic acid delta 7

spinqualitylabelsall models 3gyu, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3gyu is a 2 chain structure with sequence from Homo sapiens and Strongyloides stercoralis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: DL7, MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9XZJ5_STRER Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Nematode parasitism is a worldwide health problem resulting in malnutrition and morbidity in over 1 billion people. The molecular mechanisms governing infection are poorly understood. Here, we report that an evolutionarily conserved nuclear hormone receptor signaling pathway governs development of the stage 3 infective larvae (iL3) in several nematode parasites, including Strongyloides stercoralis, Ancylostoma spp., and Necator americanus. As in the free-living Caenorhabditis elegans, steroid hormone-like dafachronic acids induced recovery of the dauer-like iL3 in parasitic nematodes by activating orthologs of the nuclear receptor DAF-12. Moreover, administration of dafachronic acid markedly reduced the pathogenic iL3 population in S. stercoralis, indicating the potential use of DAF-12 ligands to treat disseminated strongyloidiasis. To understand the pharmacology of targeting DAF-12, we solved the 3-dimensional structure of the S. stercoralis DAF-12 ligand-binding domain cocrystallized with dafachronic acids. These results reveal the molecular basis for DAF-12 ligand binding and identify nuclear receptors as unique therapeutic targets in parasitic nematodes. Identification of the nuclear receptor DAF-12 as a therapeutic target in parasitic nematodes.,Wang Z, Zhou XE, Motola DL, Gao X, Suino-Powell K, Conneely A, Ogata C, Sharma KK, Auchus RJ, Lok JB, Hawdon JM, Kliewer SA, Xu HE, Mangelsdorf DJ Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9138-43. Epub 2009 Jun 2. PMID:19497877 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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