2pgz: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of Cocaine bound to an ACh-Binding Protein== | ==Crystal structure of Cocaine bound to an ACh-Binding Protein== | ||
<StructureSection load='2pgz' size='340' side='right' caption='[[2pgz]], [[Resolution|resolution]] 1.76Å' scene=''> | <StructureSection load='2pgz' size='340' side='right' caption='[[2pgz]], [[Resolution|resolution]] 1.76Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2pgz]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Aplca Aplca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PGZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PGZ FirstGlance]. <br> | <table><tr><td colspan='2'>[[2pgz]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Aplca Aplca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PGZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PGZ FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=COC:COCAINE'>COC</scene>, <scene name='pdbligand= | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=COC:COCAINE'>COC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">synthetic ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6500 APLCA])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">synthetic ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6500 APLCA])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pgz OCA], [http://pdbe.org/2pgz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2pgz RCSB], [http://www.ebi.ac.uk/pdbsum/2pgz PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pgz OCA], [http://pdbe.org/2pgz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2pgz RCSB], [http://www.ebi.ac.uk/pdbsum/2pgz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2pgz ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
| Line 15: | Line 16: | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2pgz ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 26: | Line 27: | ||
</div> | </div> | ||
<div class="pdbe-citations 2pgz" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 2pgz" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 39: | Line 37: | ||
[[Category: Benzodiazepine]] | [[Category: Benzodiazepine]] | ||
[[Category: Choline binding protein]] | [[Category: Choline binding protein]] | ||
[[Category: Choline-binding protein]] | |||
[[Category: Cocaine]] | [[Category: Cocaine]] | ||
[[Category: Galanthamine]] | [[Category: Galanthamine]] | ||
[[Category: Nicotinic acetycholine receptor]] | [[Category: Nicotinic acetycholine receptor]] | ||
[[Category: Non-competitive inhibitor]] | [[Category: Non-competitive inhibitor]] | ||
Revision as of 12:25, 18 October 2017
Crystal structure of Cocaine bound to an ACh-Binding ProteinCrystal structure of Cocaine bound to an ACh-Binding Protein
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedRapid neurotransmission is mediated through a superfamily of Cys-loop receptors that includes the nicotinic acetylcholine (nAChR), gamma-aminobutyric acid (GABA(A)), serotonin (5-HT(3)) and glycine receptors. A class of ligands, including galanthamine, local anesthetics and certain toxins, interact with nAChRs non-competitively. Suggested modes of action include blockade of the ion channel, modulation from undefined extracellular sites, stabilization of desensitized states, and association with annular or boundary lipid. Alignment of mammalian Cys-loop receptors shows aromatic residues, found in the acetylcholine or ligand-binding pocket of nAChRs, are conserved in all subunit interfaces of neuronal nAChRs, including those that are not formed by alpha subunits on the principal side of the transmitter binding site. The amino-terminal domain containing the ligand recognition site is homologous to the soluble acetylcholine-binding protein (AChBP) from mollusks, an established structural and functional surrogate. We assess ligand specificity and employ X-ray crystallography with AChBP to demonstrate ligand interactions at subunit interfaces lacking vicinal cysteines (i.e. the non-alpha subunit interfaces in nAChRs). Non-competitive nicotinic ligands bind AChBP with high affinity (K(d) 0.015-6 microM). We mutated the vicinal cysteine residues in loop C of AChBP to mimic the non-alpha subunit interfaces of neuronal nAChRs and other Cys loop receptors. Classical nicotinic agonists show a 10-40-fold reduction in binding affinity, whereas binding of ligands known to be non-competitive are not affected. X-ray structures of cocaine and galanthamine bound to AChBP (1.8 A and 2.9 A resolution, respectively) reveal interactions deep within the subunit interface and the absence of a contact surface with the tip of loop C. Hence, in addition to channel blocking, non-competitive interactions with heteromeric neuronal nAChR appear to occur at the non-alpha subunit interface, a site presumed to be similar to that of modulating benzodiazepines on GABA(A) receptors. Galanthamine and non-competitive inhibitor binding to ACh-binding protein: evidence for a binding site on non-alpha-subunit interfaces of heteromeric neuronal nicotinic receptors.,Hansen SB, Taylor P J Mol Biol. 2007 Jun 15;369(4):895-901. Epub 2007 Mar 31. PMID:17481657[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||