3GYT

Nuclear receptor DAF-12 from parasitic nematode Strongyloides stercoralis in complex with its physiological ligand dafachronic acid delta 4

3GYT の概要

• エントリーDOI: 10.2210/pdb3gyt/pdb
• 関連するPDBエントリー: 3GYU
• 分子名称: Nuclear hormone receptor of the steroid/thyroid hormone receptors superfamily, SRC1, (14beta,17alpha,25R)-3-oxocholest-4-en-26-oic acid, ... (4 entities in total)
• 機能のキーワード: nuclear receptor, ligand binding domain, dafachronic acid, src1, nematode, strongyloides stercoralis, dna-binding, metal-binding, nucleus, receptor, transcription, transcription regulation, zinc, zinc-finger
• 由来する生物種: Strongyloides stercoralis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29713.19

構造登録者

Zhou, X.E.,Wang, Z.,Suino-Powell, K.,Motola, D.L.,Conneely, A.,Ogata, C.,Sharma, K.K.,Auchus, R.J.,Kliewer, S.A.,Xu, H.E.,Mangelsdorf, D.J. (登録日: 2009-04-05, 公開日: 2009-07-07, 最終更新日: 2024-02-21)

主引用文献

Wang, Z.,Zhou, X.E.,Motola, D.L.,Gao, X.,Suino-Powell, K.,Conneely, A.,Ogata, C.,Sharma, K.K.,Auchus, R.J.,Lok, J.B.,Hawdon, J.M.,Kliewer, S.A.,Xu, H.E.,Mangelsdorf, D.J.
Identification of the nuclear receptor DAF-12 as a therapeutic target in parasitic nematodes.
Proc.Natl.Acad.Sci.USA, 106:9138-9143, 2009

PubMed Abstract: 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.

PubMed: 19497877
DOI: 10.1073/pnas.0904064106

実験手法

X-RAY DIFFRACTION (2.4 Å)