1kl8

NMR STRUCTURAL ANALYSIS OF THE COMPLEX FORMED BETWEEN ALPHA-BUNGAROTOXIN AND THE PRINCIPAL ALPHA-NEUROTOXIN BINDING SEQUENCE ON THE ALPHA7 SUBUNIT OF A NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR

Structural highlights

1kl8 is a 2 chain structure with sequence from Bungarus multicinctus and Gallus gallus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Ligands:	HSL
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

3L21A_BUNMU Binds with high affinity to muscular (tested on Torpedo marmorata, Kd=0.4 nM) and neuronal (tested on chimeric alpha-7/CHRNA7, Kd=0.95 nM) nicotinic acetylcholine receptor (nAChR) and inhibits acetylcholine from binding to the receptor, thereby impairing neuromuscular and neuronal transmission (PubMed:9305882). It also shows an activity on GABA(A) receptors (PubMed:16549768, PubMed:25634239). It antagonises GABA-activated currents with high potency when tested on primary hippocampal neurons (PubMed:25634239). It inhibits recombinantly expressed GABA(A) receptors composed of alpha-2-beta-2-gamma-2 (GABRA2-GABRB2-GABRG2) subunits with high potency (62.3% inhibition at 20 uM of toxin) (PubMed:25634239). It also shows a weaker inhibition on GABA(A) receptors composed of alpha-1-beta-2-gamma-2 (GABRA1-GABRB2-GABRG2) subunits, alpha-4-beta-2-gamma-2 (GABRA4-GABRB2-GABRG2) subunits, and alpha-5-beta-2-gamma-2 (GABRA5-GABRB2-GABRG2) subunits (PubMed:25634239). A very weak inhibition is also observed on GABA(A) receptor composed of alpha-1-beta-3-gamma-2 (GABRA1-GABRB3-GABRG2) (PubMed:26221036). It has also been shown to bind and inhibit recombinant GABA(A) receptor beta-3/GABRB3 subunit (Kd=about 50 nM) (PubMed:16549768). In addition, it blocks the extracellular increase of dopamine evoked by nicotine only at the higher dose (4.2 uM) (PubMed:9840221).^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

↑ McCann CM, Bracamontes J, Steinbach JH, Sanes JR. The cholinergic antagonist alpha-bungarotoxin also binds and blocks a subset of GABA receptors. Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5149-54. doi:, 10.1073/pnas.0600847103. Epub 2006 Mar 20. PMID:16549768 doi:https://dx.doi.org/10.1073/pnas.0600847103
↑ Hannan S, Mortensen M, Smart TG. Snake neurotoxin alpha-bungarotoxin is an antagonist at native GABA(A) receptors. Neuropharmacology. 2015 Jun;93:28-40. doi: 10.1016/j.neuropharm.2015.01.001. Epub, 2015 Jan 26. PMID:25634239 doi:https://dx.doi.org/10.1016/j.neuropharm.2015.01.001
↑ Servent D, Winckler-Dietrich V, Hu HY, Kessler P, Drevet P, Bertrand D, Menez A. Only snake curaremimetic toxins with a fifth disulfide bond have high affinity for the neuronal alpha7 nicotinic receptor. J Biol Chem. 1997 Sep 26;272(39):24279-86. PMID:9305882
↑ Dajas-Bailador F, Costa G, Dajas F, Emmett S. Effects of alpha-erabutoxin, alpha-bungarotoxin, alpha-cobratoxin and fasciculin on the nicotine-evoked release of dopamine in the rat striatum in vivo. Neurochem Int. 1998 Oct;33(4):307-12. PMID:9840221

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OCA

[1] McCann CM, Bracamontes J, Steinbach JH, Sanes JR. The cholinergic antagonist alpha-bungarotoxin also binds and blocks a subset of GABA receptors. Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5149-54. doi:, 10.1073/pnas.0600847103. Epub 2006 Mar 20. PMID:16549768 doi:https://dx.doi.org/10.1073/pnas.0600847103

[2] Hannan S, Mortensen M, Smart TG. Snake neurotoxin alpha-bungarotoxin is an antagonist at native GABA(A) receptors. Neuropharmacology. 2015 Jun;93:28-40. doi: 10.1016/j.neuropharm.2015.01.001. Epub, 2015 Jan 26. PMID:25634239 doi:https://dx.doi.org/10.1016/j.neuropharm.2015.01.001

[3] Servent D, Winckler-Dietrich V, Hu HY, Kessler P, Drevet P, Bertrand D, Menez A. Only snake curaremimetic toxins with a fifth disulfide bond have high affinity for the neuronal alpha7 nicotinic receptor. J Biol Chem. 1997 Sep 26;272(39):24279-86. PMID:9305882

[4] Dajas-Bailador F, Costa G, Dajas F, Emmett S. Effects of alpha-erabutoxin, alpha-bungarotoxin, alpha-cobratoxin and fasciculin on the nicotine-evoked release of dopamine in the rat striatum in vivo. Neurochem Int. 1998 Oct;33(4):307-12. PMID:9840221

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[2]

[3]

[4]

1kl8

NMR STRUCTURAL ANALYSIS OF THE COMPLEX FORMED BETWEEN ALPHA-BUNGAROTOXIN AND THE PRINCIPAL ALPHA-NEUROTOXIN BINDING SEQUENCE ON THE ALPHA7 SUBUNIT OF A NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR

Structural highlights

Function

Evolutionary Conservation

See Also

References

Contents

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