4w63: Difference between revisions
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<StructureSection load='4w63' size='340' side='right'caption='[[4w63]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='4w63' size='340' side='right'caption='[[4w63]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4w63]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4w63]] 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=4W63 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4W63 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HTB:N-(1-BENZOFURAN-2-YLMETHYL)-N-(1,2,3,4-TETRAHYDROACRIDIN-9-YL)HEPTANE-1,7-DIAMINE'>HTB</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HTB:N-(1-BENZOFURAN-2-YLMETHYL)-N-(1,2,3,4-TETRAHYDROACRIDIN-9-YL)HEPTANE-1,7-DIAMINE'>HTB</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4w63 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4w63 OCA], [https://pdbe.org/4w63 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4w63 RCSB], [https://www.ebi.ac.uk/pdbsum/4w63 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4w63 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [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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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Tetronarce californica]] | ||
[[Category: Lamba | [[Category: Lamba D]] | ||
[[Category: Pesaresi | [[Category: Pesaresi A]] | ||
[[Category: Samez | [[Category: Samez S]] | ||
Latest revision as of 13:40, 10 January 2024
TORPEDO CALIFORNICA ACETYLCHOLINESTERASE IN COMPLEX WITH A TACRINE-BENZOFURAN HYBRID INHIBITORTORPEDO CALIFORNICA ACETYLCHOLINESTERASE IN COMPLEX WITH A TACRINE-BENZOFURAN HYBRID INHIBITOR
Structural highlights
FunctionACES_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 PubMedTwenty-six new tacrine-benzofuran hybrids were designed, synthesized, and evaluated in vitro on key molecular targets for Alzheimer's disease. Most hybrids exhibited good inhibitory activities on cholinesterases and beta-amyloid self-aggregation. Selected compounds displayed significant inhibition of human beta-secretase-1 (hBACE-1). Among the 26 hybrids, 2e showed the most interesting profile as a subnanomolar selective inhibitor of human acetylcholinesterase (hAChE) (IC50 = 0.86 nM) and a good inhibitor of both beta-amyloid aggregation (hAChE- and self-induced, 61.3% and 58.4%, respectively) and hBACE-1 activity (IC50 = 1.35 muM). Kinetic studies showed that 2e acted as a slow, tight-binding, mixed-type inhibitor, while X-ray crystallographic studies highlighted the ability of 2e to induce large-scale structural changes in the active-site gorge of Torpedo californica AChE (TcAChE), with significant implications for structure-based drug design. In vivo studies confirmed that 2e significantly ameliorates performances of scopolamine-treated ICR mice. Finally, 2e administration did not exhibit significant hepatotoxicity. Novel Tacrine-Benzofuran Hybrids as Potent Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease: Design, Synthesis, Biological Evaluation, and X-ray Crystallography.,Zha X, Lamba D, Zhang L, Lou Y, Xu C, Kang D, Chen L, Xu Y, Zhang L, De Simone A, Samez S, Pesaresi A, Stojan J, Lopez MG, Egea J, Andrisano V, Bartolini M J Med Chem. 2016 Jan 14;59(1):114-31. doi: 10.1021/acs.jmedchem.5b01119. Epub, 2015 Dec 29. PMID:26632651[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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