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2pgz

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Crystal structure of Cocaine bound to an ACh-Binding Protein

Structural highlights

2pgz is a 5 chain structure with sequence from Aplysia californica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.76Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q8WSF8_APLCA

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 PubMed

Rapid 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

↑ Hansen SB, Taylor P. 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. J Mol Biol. 2007 Jun 15;369(4):895-901. Epub 2007 Mar 31. PMID:17481657 doi:10.1016/j.jmb.2007.03.067

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2pgz"

Categories: Aplysia californica | Large Structures | Hansen SB | Taylor P

@@ Line 1: / Line 1: @@
 ==Crystal structure of Cocaine bound to an ACh-Binding Protein==
-<StructureSection load='2pgz' size='340' side='right' caption='[[2pgz]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
+<StructureSection load='2pgz' size='340' side='right'caption='[[2pgz]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
 == 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 [https://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica]. 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 [https://proteopedia.org/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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.76&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='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'>[https://proteopedia.org/fgij/fg.htm?mol=2pgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pgz OCA], [https://pdbe.org/2pgz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pgz RCSB], [https://www.ebi.ac.uk/pdbsum/2pgz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pgz ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q8WSF8_APLCA Q8WSF8_APLCA]
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pg/2pgz_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pg/2pgz_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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="background-color:#fffaf0;">
@@ Line 28: / Line 31: @@
 ==See Also==
-*[[Acetylcholine binding protein|Acetylcholine binding protein]]
+*[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Aplca]]
+[[Category: Aplysia californica]]
-[[Category: Hansen, S B]]
+[[Category: Large Structures]]
-[[Category: Taylor, P]]
+[[Category: Hansen SB]]
-[[Category: Acetycholine-binding protein]]
+[[Category: Taylor P]]
-[[Category: Benzodiazepine]]
-[[Category: Choline binding protein]]
-[[Category: Cocaine]]
-[[Category: Galanthamine]]
-[[Category: Nicotinic acetycholine receptor]]
-[[Category: Non-competitive inhibitor]]

2pgz

From Proteopedia

Current revision

Crystal structure of Cocaine bound to an ACh-Binding Protein

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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