Water-soluble ligand-binding proteins and analogs of...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/11 (2006.01) A61K 38/16 (2006.01) A61K 47/48 (2006.01) C07K 1/00 (2006.01) C07K 14/435 (2006.01) C07K 14/705 (2006.01) C07K 16/00 (2006.01) C07K 19/00 (2006.01) C12N 5/10 (2006.01) C12N 15/63 (2006.01) C12Q 1/68 (2006.01) G01N 33/53 (2006.01) G01N 33/566 (2006.01)

Patent

CA 2331876

Provided are water-soluble ligand-binding proteins derived from molluscs and analogs of ligand-gated ion channels, crystals thereof and their use for screening ligands of ligand-gated ion channels. In particular, water-soluble ligand- binding proteins are provided that are capable of forming multimers and are amenable to crystallization. The crystal structure of one these proteins, an acetylcholine binding protein (AChBP) is provided, which can be used to generate 3D models of the extracellular ligand-binding domain of ligand-gated ion channels and thus for screening of drugs that act on these ion channels. Furthermore, chimeric proteins are provided that are capable of binding a ligand of a ligand-gated receptor, and comprising at least the amino acids of the AChBP determining solubility of the AChBP, in the same positions as in the AChBP, and furthermore comprising amino acids determining binding to said ligand.

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