5H9N

Crystal structure of LTBP1 Y114A mutant in complex with leukotriene C4

Summary for 5H9N

• Entry DOI: 10.2210/pdb5h9n/pdb
• Related: 5H9L 5HA0 5HAE
• Descriptor: Lipocalin AI-4, (5~{S},6~{R},7~{E},9~{E},11~{Z},14~{Z})-6-[(2~{R})-2-[[(4~{S})-4-azanyl-5-oxidanyl-5-oxidanylidene-pentanoyl]amino]-3-( 2-hydroxy-2-oxoethylamino)-3-oxidanylidene-propyl]sulfanyl-5-oxidanyl-icosa-7,9,11,14-tetraenoic acid (3 entities in total)
• Functional Keywords: lipocalin, rhodnius, salivary, transport protein
• Biological source: Rhodnius prolixus (Triatomid bug)
• Total number of polymer chains: 1
• Total formula weight: 17438.39

Authors

Andersen, J.F. (deposition date: 2015-12-28, release date: 2016-05-11, Last modification date: 2024-11-06)

Primary citation

Jablonka, W.,Pham, V.,Nardone, G.,Gittis, A.,Silva-Cardoso, L.,Atella, G.C.,Ribeiro, J.M.,Andersen, J.F.
Structure and Ligand-Binding Mechanism of a Cysteinyl Leukotriene-Binding Protein from a Blood-Feeding Disease Vector.
Acs Chem.Biol., 11:1934-1944, 2016

PubMed Abstract: 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. Chromatographic analysis of bound ligands showed only intact LTC4, suggesting that cleavage could be radiation-mediated.

PubMed: 27124118
DOI: 10.1021/acschembio.6b00032

Experimental method

X-RAY DIFFRACTION (1.28 Å)