View source for 1acj

==QUATERNARY LIGAND BINDING TO AROMATIC RESIDUES IN THE ACTIVE-SITE GORGE OF ACETYLCHOLINESTERASE==
<StructureSection load='1acj_au' size='340' side='right' caption='[[1acj]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1acj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pacific_electric_ray Pacific electric ray]. The June 2004 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Acetylcholinesterase''  by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2004_6 10.2210/rcsb_pdb/mom_2004_6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ACJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ACJ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=THA:TACRINE'>THA</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.7 3.1.1.7] </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=1acj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1acj OCA], [http://pdbe.org/1acj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1acj RCSB], [http://www.ebi.ac.uk/pdbsum/1acj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1acj ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/ACES_TORCA ACES_TORCA]] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions. 
== 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/ac/1acj_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/main_output.php?pdb_ID=1acj ConSurf].
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== Publication Abstract from PubMed ==
Binding sites of Torpedo acetylcholinesterase (EC 3.1.1.7) for quaternary ligands were investigated by x-ray crystallography and photoaffinity labeling. Crystal structures of complexes with ligands were determined at 2.8-A resolution. In a complex with edrophonium, and quaternary nitrogen of the ligand interacts with the indole of Trp-84, and its m-hydroxyl displays bifurcated hydrogen bonding to two members of the catalytic triad, Ser-200 and His-440. In a complex with tacrine, the acridine is stacked against the indole of Trp-84. The bisquaternary ligand decamethonium is oriented along the narrow gorge leading to the active site; one quaternary group is apposed to the indole of Trp-84 and the other to that of Trp-279, near the top of the gorge. The only major conformational difference between the three complexes is in the orientation of the phenyl ring of Phe-330. In the decamethonium complex it lies parallel to the surface of the gorge; in the other two complexes it is positioned to make contact with the bound ligand. This close interaction was confirmed by photoaffinity labelling by the photosensitive probe 3H-labeled p-(N,N-dimethylamino)benzenediazonium fluoroborate, which labeled, predominantly, Phe-330 within the active site. Labeling of Trp-279 was also observed. One mole of label is incorporated per mole of AcChoEase inactivated, indicating that labeling of Trp-279 and that of Phe-330 are mutually exclusive. The structural and chemical data, together, show the important role of aromatic groups as binding sites for quaternary ligands, and they provide complementary evidence assigning Trp-84 and Phe-330 to the "anionic" subsite of the active site and Trp-279 to the "peripheral" anionic site.

Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase.,Harel M, Schalk I, Ehret-Sabatier L, Bouet F, Goeldner M, Hirth C, Axelsen PH, Silman I, Sussman JL Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9031-5. PMID:8415649<ref>PMID:8415649</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[AChE inhibitors and substrates|AChE inhibitors and substrates]]
*[[Acetylcholinesterase|Acetylcholinesterase]]
*[[Acetylcholinesterase complexed with N-9-(1'%2C2'%2C3'%2C4'-tetrahydroacridinyl)-1%2C8-diaminooctane|Acetylcholinesterase complexed with N-9-(1'%2C2'%2C3'%2C4'-tetrahydroacridinyl)-1%2C8-diaminooctane]]
*[[Torpedo Californica Acetylcholinesterase in complex with an (R)-Tacrine-(10)-Hupyridone inhibitor|Torpedo Californica Acetylcholinesterase in complex with an (R)-Tacrine-(10)-Hupyridone inhibitor]]
*[[Torpedo californica acetylcholinesterase with alkylene-linked tacrine dimer (5 carbon linker)|Torpedo californica acetylcholinesterase with alkylene-linked tacrine dimer (5 carbon linker)]]
*[[Torpedo californica acetylcholinesterase with alkylene-linked tacrine dimer (7 carbon linker)|Torpedo californica acetylcholinesterase with alkylene-linked tacrine dimer (7 carbon linker)]]
*[[3D structures of acetylcholinesterase|3D structures of acetylcholinesterase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Acetylcholinesterase]]
[[Category: Pacific electric ray]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Harel, M]]
[[Category: Silman, I]]
[[Category: Sussman, J L]]