8bxw

Crystal structure of Odorant Binding Protein 5 from Anopheles gambiae (AgamOBP5) with Carvacrol

spinqualitylabelsall models 8bxw, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8bxw is a 1 chain structure with sequence from Anopheles gambiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.3Å Ligands: 1BO, MPD, NA, PGR, S5V Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8T6R6_ANOGA Publication Abstract from PubMed Among several proteins participating in the olfactory perception process of insects, Odorant Binding Proteins (OBPs) are today considered valid targets for the discovery of compounds that interfere with their host-detection behavior. The 3D structures of Anopheles gambiae mosquito AgamOBP1 in complex with the known synthetic repellents DEET and Icaridin have provided valuable information on the structural characteristics that govern their selective binding. However, no structure of a plant-derived repellent bound to an OBP has been available until now. Herein, we present the novel three-dimensional crystal structures of AgamOBP5 in complex with two natural phenolic monoterpenoid repellents, Carvacrol and Thymol, and the MPD molecule. Structural analysis revealed that both monoterpenoids occupy a binding site (Site-1) by adopting two alternative conformations. An additional Carvacrol was also bound to a secondary site (Site-2) near the central cavity entrance. A protein-ligand hydrogen-bond network supplemented by van der Waals interactions spans the entire binding cavity, bridging alpha4, alpha6, and alpha3 helices and stabilizing the overall structure. Fluorescence competition and Differential Scanning Calorimetry experiments verified the presence of two binding sites and the stabilization effect on AgamOBP5. While Carvacrol and Thymol bind to Site-1 with equal affinity in the submicromolar range, they exhibit a significantly lower and distinct binding capacity for Site-2 with Kd's of ~7 muMu and ~18 muMu, respectively. Finally, a comparison of AgamOBP5 complexes with the AgamOBP4-Indole structure revealed that variations of ligand-interacting aminoacids such as A109T, I72M, A112L, and A105T cause two structurally similar and homologous proteins to display different binding specificities. The structure of AgamOBP5 in complex with the natural insect repellents Carvacrol and Thymol: Crystallographic, fluorescence and thermodynamic binding studies.,Liggri PGV, Tsitsanou KE, Stamati ECV, Saitta F, Drakou CE, Leonidas DD, Fessas D, Zographos SE Int J Biol Macromol. 2023 May 15;237:124009. doi: 10.1016/j.ijbiomac.2023.124009. , Epub 2023 Mar 13. PMID:36921814 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Odorant binding protein 3D structures

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