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| - | [[Image:2uz6.jpg|left|200px]] | + | {{Seed}} |
| | + | [[Image:2uz6.png|left|200px]] |
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| | {{STRUCTURE_2uz6| PDB=2uz6 | SCENE= }} | | {{STRUCTURE_2uz6| PDB=2uz6 | SCENE= }} |
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| - | '''ACHBP-TARGETED A-CONOTOXIN CORRELATES DISTINCT BINDING ORIENTATIONS WITH NACHR SUBTYPE SELECTIVITY.'''
| + | ===ACHBP-TARGETED A-CONOTOXIN CORRELATES DISTINCT BINDING ORIENTATIONS WITH NACHR SUBTYPE SELECTIVITY.=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_17660751}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17660751 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17660751}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Receptor]] | | [[Category: Receptor]] |
| | [[Category: Soluble acetylcholine receptor]] | | [[Category: Soluble acetylcholine receptor]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 17:51:21 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 14:23:59 2008'' |
Revision as of 11:24, 29 July 2008
Template:STRUCTURE 2uz6
ACHBP-TARGETED A-CONOTOXIN CORRELATES DISTINCT BINDING ORIENTATIONS WITH NACHR SUBTYPE SELECTIVITY.
Template:ABSTRACT PUBMED 17660751
About this Structure
2UZ6 is a Protein complex structure of sequences from Aplysia californica. 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 Aug 22;26(16):3858-67. Epub 2007 Jul 26. PMID:17660751
Page seeded by OCA on Tue Jul 29 14:23:59 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. | Receptor | Soluble acetylcholine receptor
