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| | ==TORPEDO CALIFORNICA ACETYLCHOLINESTERASE IN COMPLEX WITH A CHLOROTACRINE-JUGLONE HYBRID INHIBITOR== | | ==TORPEDO CALIFORNICA ACETYLCHOLINESTERASE IN COMPLEX WITH A CHLOROTACRINE-JUGLONE HYBRID INHIBITOR== |
| - | <StructureSection load='4tvk' size='340' side='right' caption='[[4tvk]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='4tvk' size='340' side='right'caption='[[4tvk]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4tvk]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Torpedo_californica Torpedo californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TVK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TVK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4tvk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Tetronarce_californica Tetronarce californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TVK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TVK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TJH:2-({2-[(6-CHLORO-1,2,3,4-TETRAHYDROACRIDIN-9-YL)AMINO]ETHYL}AMINO)-5-HYDROXYNAPHTHALENE-1,4-DIONE'>TJH</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TJH:2-({2-[(6-CHLORO-1,2,3,4-TETRAHYDROACRIDIN-9-YL)AMINO]ETHYL}AMINO)-5-HYDROXYNAPHTHALENE-1,4-DIONE'>TJH</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'>[https://proteopedia.org/fgij/fg.htm?mol=4tvk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tvk OCA], [https://pdbe.org/4tvk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tvk RCSB], [https://www.ebi.ac.uk/pdbsum/4tvk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tvk ProSAT]</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=4tvk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tvk OCA], [http://pdbe.org/4tvk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4tvk RCSB], [http://www.ebi.ac.uk/pdbsum/4tvk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4tvk ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == 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. | + | [https://www.uniprot.org/uniprot/ACES_TETCF ACES_TETCF] 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. |
| | <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: Large Structures]] |
| - | [[Category: Torpedo californica]] | + | [[Category: Tetronarce californica]] |
| - | [[Category: Lamba, D]] | + | [[Category: Lamba D]] |
| - | [[Category: Pesaresi, A]] | + | [[Category: Pesaresi A]] |
| - | [[Category: Samez, S]] | + | [[Category: Samez S]] |
| - | [[Category: Enzyme-inhibitor complex]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Multitarget drug]]
| + | |
| - | [[Category: Quinone]]
| + | |
| - | [[Category: Tacrine]]
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| Structural highlights
Function
ACES_TETCF 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.
Publication Abstract from PubMed
We report the identification of multitarget anti-Alzheimer compounds designed by combining a naphthoquinone function and a tacrine fragment. In vitro, 12-29 displayed excellent acetylcholinesterase (AChE) inhibitory potencies and interesting capabilities to block amyloid-beta (Abeta) aggregation. The X-ray analysis of AChE-20 complex allowed rationalizing the outstanding activity data (IC50 = 0.72 nM). Selected compounds 16 and 20 showed negligible toxicity in immortalized mouse cortical neurons Neuro2A and primary rat cerebellar granule neurons. However, only 16 was less hepatotoxic than tacrine in HepG2 cells. In T67 cells, 16 and 20 showed antioxidant activity, following NQO1 induction. Furthermore in Neuro2A, they were able to completely revert the decrease in viability induced by Abeta. Importantly, they crossed the blood-brain barrier, as demonstrated in ex vivo experiments with rats. When ex vivo results were combined with in vitro studies, 16 and 20 emerged to be promising multitarget lead candidates worthy of further pursuit.
Multitarget drug design strategy: quinone-tacrine hybrids designed to block amyloid-beta aggregation and to exert anticholinesterase and antioxidant effects.,Nepovimova E, Uliassi E, Korabecny J, Pena-Altamira LE, Samez S, Pesaresi A, Garcia GE, Bartolini M, Andrisano V, Bergamini C, Fato R, Lamba D, Roberti M, Kuca K, Monti B, Bolognesi ML J Med Chem. 2014 Sep 26. PMID:25259726[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nepovimova E, Uliassi E, Korabecny J, Pena-Altamira LE, Samez S, Pesaresi A, Garcia GE, Bartolini M, Andrisano V, Bergamini C, Fato R, Lamba D, Roberti M, Kuca K, Monti B, Bolognesi ML. Multitarget drug design strategy: quinone-tacrine hybrids designed to block amyloid-beta aggregation and to exert anticholinesterase and antioxidant effects. J Med Chem. 2014 Sep 26. PMID:25259726 doi:http://dx.doi.org/10.1021/jm5010804
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