3dye
Crystal structure of AED7-norepineprhine complex
Structural highlights
FunctionD7L1_AEDAE Modulates blood feeding of female mosquitoes on vertebrate species by binding and sequestering different mediators involved in the host response, such as biogenic amines and eicosanoids (PubMed:32799410, PubMed:37909749). Binds serotonin, histamine, leukotriene B4, leukotriene C4, leukotriene D4, leukotriene E4, adrenaline and noradrenaline (PubMed:16301315, PubMed:19234127, PubMed:32799410). Does not bind tryptamine and U-46619, a stable analog of thromboxane A2 (PubMed:19234127, PubMed:32799410). Exhibits vasodilating activity (PubMed:32799410). Inhibits agonist-induced platelet aggregation but not blood clotting (PubMed:32799410). Inhibits noradrenaline-induced smooth muscle contraction (PubMed:16301315). Promotes an influx of host neutrophils at the inoculation site (PubMed:38378891).[1] [2] [3] [4] [5] (Microbial infection) Probably promotes Plasmodium gallinaceum oocyst development in mosquito midgut.[6] (Microbial infection) Exhibits antiviral activity against dengue virus type 2 probably through a direct interaction with dengue virus virions.[7] 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 PubMedThe mosquito D7 salivary proteins are encoded by a multigene family related to the arthropod odorant-binding protein (OBP) superfamily. Forms having either one or two OBP domains are found in mosquito saliva. Four single-domain and one two-domain D7 proteins from Anopheles gambiae and Aedes aegypti (AeD7), respectively, were shown to bind biogenic amines with high affinity and with a stoichiometry of one ligand per protein molecule. Sequence comparisons indicated that only the C-terminal domain of AeD7 is homologous to the single-domain proteins from A. gambiae, suggesting that the N-terminal domain may bind a different class of ligands. Here, we describe the 3D structure of AeD7 and examine the ligand-binding characteristics of the N- and C-terminal domains. Isothermal titration calorimetry and ligand complex crystal structures show that the N-terminal domain binds cysteinyl leukotrienes (cysLTs) with high affinities (50-60 nM) whereas the C-terminal domain binds biogenic amines. The lipid chain of the cysLT binds in a hydrophobic pocket of the N-terminal domain, whereas binding of norepinephrine leads to an ordering of the C-terminal portion of the C-terminal domain into an alpha-helix that, along with rotations of Arg-176 and Glu-268 side chains, acts to bury the bound ligand. Multifunctionality and mechanism of ligand binding in a mosquito antiinflammatory protein.,Calvo E, Mans BJ, Ribeiro JM, Andersen JF Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3728-33. Epub 2009 Feb 20. PMID:19234127[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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