1ux2: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
Nicotinic acetylcholine receptors are prototypes for the pharmaceutically | Nicotinic acetylcholine receptors are prototypes for the pharmaceutically important family of pentameric ligand-gated ion channels. Here we present atomic resolution structures of nicotine and carbamylcholine binding to AChBP, a water-soluble homolog of the ligand binding domain of nicotinic receptors and their family members, GABAA, GABAC, 5HT3 serotonin, and glycine receptors. Ligand binding is driven by enthalpy and is accompanied by conformational changes in the ligand binding site. Residues in the binding site contract around the ligand, with the largest movement in the C loop. As expected, the binding is characterized by substantial aromatic and hydrophobic contributions, but additionally there are close contacts between protein oxygens and positively charged groups in the ligands. The higher affinity of nicotine is due to a main chain hydrogen bond with the B loop and a closer packing of the aromatic groups. These structures will be useful tools for the development of new drugs involving nicotinic acetylcholine receptor-associated diseases. | ||
==About this Structure== | ==About this Structure== | ||
| Line 14: | Line 14: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Brejc, K.]] | [[Category: Brejc, K.]] | ||
[[Category: Celie, P | [[Category: Celie, P H.N.]] | ||
[[Category: Dijk, W | [[Category: Dijk, W J.Van.]] | ||
[[Category: Rossum-Fikkert, S | [[Category: Rossum-Fikkert, S E.Van.]] | ||
[[Category: Sixma, T | [[Category: Sixma, T K.]] | ||
[[Category: Smit, A | [[Category: Smit, A B.]] | ||
[[Category: EPE]] | [[Category: EPE]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
| Line 29: | Line 29: | ||
[[Category: pentamer]] | [[Category: pentamer]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:29:15 2008'' | ||
Revision as of 16:29, 21 February 2008
|
X-RAY STRUCTURE OF ACETYLCHOLINE BINDING PROTEIN (ACHBP)
OverviewOverview
Nicotinic acetylcholine receptors are prototypes for the pharmaceutically important family of pentameric ligand-gated ion channels. Here we present atomic resolution structures of nicotine and carbamylcholine binding to AChBP, a water-soluble homolog of the ligand binding domain of nicotinic receptors and their family members, GABAA, GABAC, 5HT3 serotonin, and glycine receptors. Ligand binding is driven by enthalpy and is accompanied by conformational changes in the ligand binding site. Residues in the binding site contract around the ligand, with the largest movement in the C loop. As expected, the binding is characterized by substantial aromatic and hydrophobic contributions, but additionally there are close contacts between protein oxygens and positively charged groups in the ligands. The higher affinity of nicotine is due to a main chain hydrogen bond with the B loop and a closer packing of the aromatic groups. These structures will be useful tools for the development of new drugs involving nicotinic acetylcholine receptor-associated diseases.
About this StructureAbout this Structure
1UX2 is a Single protein structure of sequence from Lymnaea stagnalis with , , and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures., Celie PH, van Rossum-Fikkert SE, van Dijk WJ, Brejc K, Smit AB, Sixma TK, Neuron. 2004 Mar 25;41(6):907-14. PMID:15046723
Page seeded by OCA on Thu Feb 21 15:29:15 2008