Structure and Ligand-Binding Mechanism of a Cysteinyl Leukotriene-Binding Protein from a Blood-Feeding Disease Vector
| العنوان: | Structure and Ligand-Binding Mechanism of a Cysteinyl Leukotriene-Binding Protein from a Blood-Feeding Disease Vector |
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| المؤلفون: | Georgia C. Atella, John F. Andersen, Apostolos G. Gittis, José M. C. Ribeiro, Lívia Silva-Cardoso, Van N. Pham, Willy Jablonka, Glenn Nardone |
| المصدر: | ACS Chemical Biology. 11:1934-1944 |
| بيانات النشر: | American Chemical Society (ACS), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Conformational change, Protein Conformation, Trypanosoma cruzi, Plasma protein binding, Calorimetry, Disease Vectors, Lipocalin, Biology, Ligands, Biochemistry, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Protein structure, Animals, Receptors, Leukotriene, Binding protein, General Medicine, respiratory system, Ligand (biochemistry), Molecular biology, Adenosine diphosphate, 030104 developmental biology, chemistry, Eicosanoid, Rhodnius, Molecular Medicine, lipids (amino acids, peptides, and proteins), 030217 neurology & neurosurgery |
| الوصف: | Blood-feeding disease vectors mitigate the negative effects of hemostasis and inflammation through the binding of small-molecule agonists of these processes by salivary proteins. In this study, a lipocalin protein family member (LTBP1) from the saliva of Rhodnius prolixus, a vector of the pathogen Trypanosoma cruzi, is shown to sequester cysteinyl leukotrienes during feeding to inhibit immediate inflammatory responses. Calorimetric binding experiments showed that LTBP1 binds leukotrienes C4 (LTC4) and D4 (LTD4) and E4 (LTE4) but not biogenic amines, adenosine diphosphate or other eicosanoid compounds. Crystal structures of ligand-free LTBP1 and its complexes with LTC4 and LTD4 reveal a conformational change during binding that brings Tyr 114 into close contact with the ligand. LTC4 is cleaved in the complex leaving free glutathione, and a C20 fatty acid. Chromatographic analysis of bound ligands showed only intact LTC4, suggesting that cleavage could be radiation-mediated. |
| تدمد: | 1554-8937 1554-8929 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::418e8d174933d2a62137de180bb7be36Test https://doi.org/10.1021/acschembio.6b00032Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....418e8d174933d2a62137de180bb7be36 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15548937 15548929 |
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