2uz6
From Proteopedia
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==About this Structure== | ==About this Structure== | ||
| - | 2UZ6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=NH2:'>NH2</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=1:Gol Binding Site For Chain G'>1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UZ6 OCA]. | + | 2UZ6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=NH2:'>NH2</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=1:Gol+Binding+Site+For+Chain+G'>1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UZ6 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: soluble acetylcholine receptor]] | [[Category: soluble acetylcholine receptor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:48:37 2008'' |
Revision as of 08:48, 3 February 2008
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ACHBP-TARGETED A-CONOTOXIN CORRELATES DISTINCT BINDING ORIENTATIONS WITH NACHR SUBTYPE SELECTIVITY.
Overview
Neuronal nAChRs are a diverse family of pentameric ion channels with wide, distribution throughout cells of the nervous and immune systems. However, the role of specific subtypes in normal and pathological states remains, poorly understood due to the lack of selective probes. Here, we used a, binding assay based on acetylcholine-binding protein (AChBP), a homolog of, the nicotinic acetylcholine ligand-binding domain, to discover a novel, alpha-conotoxin (alpha-TxIA) in the venom of Conus textile. alpha-TxIA, bound with high affinity to AChBPs from different species and selectively, targeted the alpha(3)beta(2) nAChR subtype. A co-crystal structure of, Ac-AChBP with the enhanced potency analog TxIA(A10L), revealed a 20, degrees backbone tilt compared to other AChBP-conotoxin complexes. This, reorientation was coordinated by a key salt bridge formed between Arg5, (TxIA) and Asp195 (Ac-AChBP). Mutagenesis studies, biochemical assays and, electrophysiological recordings directly correlated the interactions, observed in the co-crystal structure to binding affinity at AChBP and, different nAChR subtypes. Together, these results establish a new, pharmacophore for the design of novel subtype-selective ligands with, therapeutic potential in nAChR-related diseases.
About this Structure
2UZ6 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.
Reference
AChBP-targeted alpha-conotoxin correlates distinct binding orientations with nAChR subtype selectivity., Dutertre S, Ulens C, Buttner R, Fish A, van Elk R, Kendel Y, Hopping G, Alewood PF, Schroeder C, Nicke A, Smit AB, Sixma TK, Lewis RJ, EMBO J. 2007 Jul 26;. PMID:17660751
Page seeded by OCA on Sun Feb 3 10:48:37 2008
Categories: Aplysia californica | Protein complex | Alewood, P.F. | Buttner, R. | Dutertre, S. | Elk, R.Van. | Fish, A. | Hopping, G. | Kendel, Y. | Lewis, R.J. | Nicke, A. | Schroeder, C. | Sixma, T.K. | Smit, A.B. | Ulens, C. | GOL | NAG | NH2 | Receptor | Soluble acetylcholine receptor
