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| | ==Structure of human acetylcholinesterase in complex with dihydrotanshinone I== | | ==Structure of human acetylcholinesterase in complex with dihydrotanshinone I== |
| - | <StructureSection load='4m0e' size='340' side='right' caption='[[4m0e]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4m0e' size='340' side='right'caption='[[4m0e]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4m0e]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M0E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M0E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4m0e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M0E FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1YL:DIHYDROTANSHINONE+I'>1YL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1YL:DIHYDROTANSHINONE+I'>1YL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4m0f|4m0f]]</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=4m0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m0e OCA], [https://pdbe.org/4m0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m0e RCSB], [https://www.ebi.ac.uk/pdbsum/4m0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m0e ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACHE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <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=4m0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m0e OCA], [http://pdbe.org/4m0e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4m0e RCSB], [http://www.ebi.ac.uk/pdbsum/4m0e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4m0e ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ACES_HUMAN ACES_HUMAN]] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.<ref>PMID:2714437</ref> <ref>PMID:1748670</ref> <ref>PMID:1517212</ref> <ref>PMID:11985878</ref> | + | [https://www.uniprot.org/uniprot/ACES_HUMAN ACES_HUMAN] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.<ref>PMID:2714437</ref> <ref>PMID:1748670</ref> <ref>PMID:1517212</ref> <ref>PMID:11985878</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Acetylcholinesterase|Acetylcholinesterase]] | + | *[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]] |
| - | *[[3D structures of acetylcholinesterase|3D structures of acetylcholinesterase]]
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Acetylcholinesterase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Cheung, J]] | + | [[Category: Cheung J]] |
| - | [[Category: Gary, E N]] | + | [[Category: Gary EN]] |
| - | [[Category: Rosenberry, T L]] | + | [[Category: Rosenberry TL]] |
| - | [[Category: Shiomi, K]] | + | [[Category: Shiomi K]] |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| Structural highlights
Function
ACES_HUMAN Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.[1] [2] [3] [4]
Publication Abstract from PubMed
Acetylcholinesterase is a critical enzyme that regulates neurotransmission by degrading the neurotransmitter acetylcholine in synapses of the nervous system. It is an important target for both therapeutic drugs that treat Alzheimer's disease and chemical warfare agents that cripple the nervous system and cause death through paralysis. The enzyme has both catalytic and peripheral sites to which inhibitors may bind. Structures of recombinant human acetylcholinesterase in complex with the natural product inhibitors dihydrotanshinone I and territrem B reveal dihydrotanshinone I binding that is specific to only the peripheral site and territrem B binding that spans both sites and distorts the protein backbone in the peripheral site. These inhibitors may function as important molecular templates for therapeutics used for treatment of disease and protection against nerve agents.
Structures of human acetylcholinesterase bound to dihydrotanshinone I and territrem B show peripheral site flexibility.,Cheung J, Gary EN, Shiomi K, Rosenberry TL ACS Med Chem Lett. 2013 Sep 23;4(11):1091-6. doi: 10.1021/ml400304w. eCollection , 2013 Nov 14. PMID:24900610[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chhajlani V, Derr D, Earles B, Schmell E, August T. Purification and partial amino acid sequence analysis of human erythrocyte acetylcholinesterase. FEBS Lett. 1989 Apr 24;247(2):279-82. PMID:2714437
- ↑ Velan B, Grosfeld H, Kronman C, Leitner M, Gozes Y, Lazar A, Flashner Y, Marcus D, Cohen S, Shafferman A. The effect of elimination of intersubunit disulfide bonds on the activity, assembly, and secretion of recombinant human acetylcholinesterase. Expression of acetylcholinesterase Cys-580----Ala mutant. J Biol Chem. 1991 Dec 15;266(35):23977-84. PMID:1748670
- ↑ Shafferman A, Kronman C, Flashner Y, Leitner M, Grosfeld H, Ordentlich A, Gozes Y, Cohen S, Ariel N, Barak D, et al.. Mutagenesis of human acetylcholinesterase. Identification of residues involved in catalytic activity and in polypeptide folding. J Biol Chem. 1992 Sep 5;267(25):17640-8. PMID:1517212
- ↑ Yang L, He HY, Zhang XJ. Increased expression of intranuclear AChE involved in apoptosis of SK-N-SH cells. Neurosci Res. 2002 Apr;42(4):261-8. PMID:11985878
- ↑ Cheung J, Gary EN, Shiomi K, Rosenberry TL. Structures of human acetylcholinesterase bound to dihydrotanshinone I and territrem B show peripheral site flexibility. ACS Med Chem Lett. 2013 Sep 23;4(11):1091-6. doi: 10.1021/ml400304w. eCollection , 2013 Nov 14. PMID:24900610 doi:http://dx.doi.org/10.1021/ml400304w
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