Structure and Ligand-Binding Mechanism of a Cysteinyl Leukotriene-Binding Protein from a Blood-Feeding Disease Vector

Jablonka, Willy; Pham, Van; Nardone, Glenn; Gittis, Apostolos; Silva-Cardoso, Lívia; Atella, Georgia C.; Ribeiro, José M. C.; Andersen, John F.

doi:10.1021/acschembio.6b00032

Title: Structure and Ligand-Binding Mechanism of a Cysteinyl Leukotriene-Binding Protein from a Blood-Feeding Disease Vector

Journal Article · Thu Apr 28 00:00:00 EDT 2016 · ACS Chemical Biology

DOI:https://doi.org/10.1021/acschembio.6b00032· OSTI ID:1267470

Jablonka, Willy ^[1]; Pham, Van ^[1]; Nardone, Glenn ^[1]; Gittis, Apostolos ^[1]; Silva-Cardoso, Lívia ^[2]; Atella, Georgia C. ^[2]; Ribeiro, José M. C. ^[1]; Andersen, John F. ^[1]

National Inst. of Health (NIH), Rockville, MD (United States)
Univ. Federal do Rio de Janeiro (Brazil)

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), 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 Tyr114 into close contact with the ligand. LTC₄ is cleaved in the complex, leaving free glutathione and a C₂₀ fatty acid. As a result, chromatographic analysis of bound ligands showed only intact LTC₄, suggesting that cleavage could be radiation-mediated.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: NIAID; National Inst. of Health; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil)

OSTI ID:: 1267470

Journal Information:: ACS Chemical Biology, Vol. 11, Issue 7; ISSN 1554-8929

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Title: Structure and Ligand-Binding Mechanism of a Cysteinyl Leukotriene-Binding Protein from a Blood-Feeding Disease Vector

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