2br8

File:2br8.gif

spinqualitylabelsall models 2br8, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF ACETYLCHOLINE-BINDING PROTEIN (ACHBP) FROM APLYSIA CALIFORNICA IN COMPLEX WITH AN ALPHA-CONOTOXIN PNIA VARIANT

OverviewOverview

Conotoxins (Ctx) form a large family of peptide toxins from cone snail, venoms that act on a broad spectrum of ion channels and receptors. The, subgroup alpha-Ctx specifically and selectively binds to subtypes of, nicotinic acetylcholine receptors (nAChRs), which are targets for, treatment of several neurological disorders. Here we present the structure, at a resolution of 2.4 A of alpha-Ctx PnIA (A10L D14K), a potent blocker, of the alpha(7)-nAChR, bound with high affinity to acetylcholine binding, protein (AChBP), the prototype for the ligand-binding domains of the nAChR, superfamily. Alpha-Ctx is buried deep within the ligand-binding site and, interacts with residues on both faces of adjacent subunits. The toxin, itself does not change conformation, but displaces the C loop of AChBP and, induces a rigid-body subunit movement. Knowledge of these contacts could, facilitate the rational design of drug leads using the Ctx framework and, may lead to compounds with increased receptor subtype selectivity.

About this StructureAbout this Structure

2BR8 is a Protein complex structure of sequences from Aplysia californica with SO4 and NH2 as ligands. Structure known Active Site: AC1. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of nicotinic acetylcholine receptor homolog AChBP in complex with an alpha-conotoxin PnIA variant., Celie PH, Kasheverov IE, Mordvintsev DY, Hogg RC, van Nierop P, van Elk R, van Rossum-Fikkert SE, Zhmak MN, Bertrand D, Tsetlin V, Sixma TK, Smit AB, Nat Struct Mol Biol. 2005 Jul;12(7):582-8. Epub 2005 Jun 12. PMID:15951818

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