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==Crystal structure of mouse acetylcholinesterase complexed with succinylcholine== | |||
<StructureSection load='2ha2' size='340' side='right'caption='[[2ha2]], [[Resolution|resolution]] 2.05Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2ha2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HA2 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=SCK:2,2-[(1,4-DIOXOBUTANE-1,4-DIYL)BIS(OXY)]BIS(N,N,N-TRIMETHYLETHANAMINIUM)'>SCK</scene>, <scene name='pdbligand=SCU:N,N,N-TRIMETHYL-2-[(4-OXOBUTANOYL)OXY]ETHANAMINIUM'>SCU</scene></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=2ha2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ha2 OCA], [https://pdbe.org/2ha2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ha2 RCSB], [https://www.ebi.ac.uk/pdbsum/2ha2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ha2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ACES_MOUSE ACES_MOUSE] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. | |||
== 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/ha/2ha2_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2ha2 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Hydrolysis of acetylcholine catalyzed by acetylcholinesterase (AChE), one of the most efficient enzymes in nature, occurs at the base of a deep and narrow active center gorge. At the entrance of the gorge, the peripheral anionic site provides a binding locus for allosteric ligands, including substrates. To date, no structural information on substrate entry to the active center from the peripheral site of AChE or its subsequent egress has been reported. Complementary crystal structures of mouse AChE and an inactive mouse AChE mutant with a substituted catalytic serine (S203A), in various complexes with four substrates (acetylcholine, acetylthiocholine, succinyldicholine, and butyrylthiocholine), two non-hydrolyzable substrate analogues (m-(N,N,N-trimethylammonio)-trifluoroacetophenone and 4-ketoamyltrimethylammonium), and one reaction product (choline) were solved in the 2.05-2.65-A resolution range. These structures, supported by binding and inhibition data obtained on the same complexes, reveal the successive positions and orientations of the substrates bound to the peripheral site and proceeding within the gorge toward the active site, the conformations of the presumed transition state for acylation and the acyl-enzyme intermediate, and the positions and orientations of the dissociating and egressing products. Moreover, the structures of the AChE mutant in complexes with acetylthiocholine and succinyldicholine reveal additional substrate binding sites on the enzyme surface, distal to the gorge entry. Hence, we provide a comprehensive set of structural snapshots of the steps leading to the intermediates of catalysis and the potential regulation by substrate binding to various allosteric sites at the enzyme surface. | |||
Substrate and product trafficking through the active center gorge of acetylcholinesterase analyzed by crystallography and equilibrium binding.,Bourne Y, Radic Z, Sulzenbacher G, Kim E, Taylor P, Marchot P J Biol Chem. 2006 Sep 29;281(39):29256-67. Epub 2006 Jul 12. PMID:16837465<ref>PMID:16837465</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2ha2" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]] | |||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Bourne Y]] | |||
[[Category: Bourne | [[Category: Kim E]] | ||
[[Category: Kim | [[Category: Marchot P]] | ||
[[Category: Marchot | [[Category: Radic Z]] | ||
[[Category: Radic | [[Category: Sulzenbacher G]] | ||
[[Category: Sulzenbacher | [[Category: Taylor P]] | ||
[[Category: Taylor | |||
Latest revision as of 10:55, 23 October 2024
Crystal structure of mouse acetylcholinesterase complexed with succinylcholineCrystal structure of mouse acetylcholinesterase complexed with succinylcholine
Structural highlights
FunctionACES_MOUSE Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. 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 PubMedHydrolysis of acetylcholine catalyzed by acetylcholinesterase (AChE), one of the most efficient enzymes in nature, occurs at the base of a deep and narrow active center gorge. At the entrance of the gorge, the peripheral anionic site provides a binding locus for allosteric ligands, including substrates. To date, no structural information on substrate entry to the active center from the peripheral site of AChE or its subsequent egress has been reported. Complementary crystal structures of mouse AChE and an inactive mouse AChE mutant with a substituted catalytic serine (S203A), in various complexes with four substrates (acetylcholine, acetylthiocholine, succinyldicholine, and butyrylthiocholine), two non-hydrolyzable substrate analogues (m-(N,N,N-trimethylammonio)-trifluoroacetophenone and 4-ketoamyltrimethylammonium), and one reaction product (choline) were solved in the 2.05-2.65-A resolution range. These structures, supported by binding and inhibition data obtained on the same complexes, reveal the successive positions and orientations of the substrates bound to the peripheral site and proceeding within the gorge toward the active site, the conformations of the presumed transition state for acylation and the acyl-enzyme intermediate, and the positions and orientations of the dissociating and egressing products. Moreover, the structures of the AChE mutant in complexes with acetylthiocholine and succinyldicholine reveal additional substrate binding sites on the enzyme surface, distal to the gorge entry. Hence, we provide a comprehensive set of structural snapshots of the steps leading to the intermediates of catalysis and the potential regulation by substrate binding to various allosteric sites at the enzyme surface. Substrate and product trafficking through the active center gorge of acetylcholinesterase analyzed by crystallography and equilibrium binding.,Bourne Y, Radic Z, Sulzenbacher G, Kim E, Taylor P, Marchot P J Biol Chem. 2006 Sep 29;281(39):29256-67. Epub 2006 Jul 12. PMID:16837465[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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