3DYE

Crystal structure of AED7-norepineprhine complex

Summary for 3DYE

• Entry DOI: 10.2210/pdb3dye/pdb
• Related: 3DY9
• Descriptor: D7 protein, BROMIDE ION, L-NOREPINEPHRINE, ... (5 entities in total)
• Functional Keywords: odorant-binding protein, all-helical, secreted, allergen
• Biological source: Aedes aegypti (Yellowfever mosquito)
• Cellular location: Secreted : P18153
• Total number of polymer chains: 1
• Total formula weight: 35882.93

Authors

Andersen, J.F.,Calvo, E.,Mans, B.J.,Ribeiro, J.M. (deposition date: 2008-07-27, release date: 2009-02-03, Last modification date: 2021-03-31)

Primary citation

Calvo, E.,Mans, B.J.,Ribeiro, J.M.,Andersen, J.F.
Multifunctionality and mechanism of ligand binding in a mosquito antiinflammatory protein
Proc.Natl.Acad.Sci.USA, 106:3728-3733, 2009

PubMed Abstract: The 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.

PubMed: 19234127
DOI: 10.1073/pnas.0813190106

Experimental method

X-RAY DIFFRACTION (1.75 Å)