2br8: Difference between revisions

Revision as of 17:40, 21 February 2008

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 and as ligands. Known structural/functional Site: . 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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OCA

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 ==Overview==
-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.
+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 Structure==
@@ Line 14: / Line 14: @@
 [[Category: Protein complex]]
 [[Category: Bertrand, D.]]
-[[Category: Celie, P.H.N.]]
+[[Category: Celie, P H.N.]]
-[[Category: Elk, R.Van.]]
+[[Category: Elk, R Van.]]
-[[Category: Hogg, R.C.]]
+[[Category: Hogg, R C.]]
-[[Category: Kasheverov, I.E.]]
+[[Category: Kasheverov, I E.]]
-[[Category: Mordvintsev, D.Y.]]
+[[Category: Mordvintsev, D Y.]]
-[[Category: Nierop, P.Van.]]
+[[Category: Nierop, P Van.]]
-[[Category: Rossum-Fikkert, S.E.Van.]]
+[[Category: Rossum-Fikkert, S E.Van.]]
-[[Category: Sixma, T.K.]]
+[[Category: Sixma, T K.]]
-[[Category: Smit, A.B.]]
+[[Category: Smit, A B.]]
 [[Category: Tsetlin, V.]]
-[[Category: Zhmak, M.N.]]
+[[Category: Zhmak, M N.]]
 [[Category: NH2]]
 [[Category: SO4]]
@@ Line 42: / Line 42: @@
 [[Category: toxin]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:26:59 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:40:51 2008''