5nap
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Torpedo californica acetylcholinesterase in complex with a non-chiral donepezil-like inhibitor 17== | |
| + | <StructureSection load='5nap' size='340' side='right' caption='[[5nap]], [[Resolution|resolution]] 2.17Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5nap]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Tetronarce_californica Tetronarce californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NAP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NAP FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=DZ7:(2~{E})-5,6-dimethoxy-2-[[1-(phenylmethyl)piperidin-4-yl]methylidene]-3~{H}-inden-1-one'>DZ7</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=5nap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nap OCA], [http://pdbe.org/5nap PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nap RCSB], [http://www.ebi.ac.uk/pdbsum/5nap PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nap ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://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;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Acetylcholinesterase inhibitors were introduced for the symptomatic treatment of Alzheimer's disease (AD). Among the currently approved inhibitors, donepezil (DNP) is one of the most preferred choices in AD therapy. The X-ray crystal structures of Torpedo californica AChE in complex with two novel rigid DNP-like analogs, compounds 1 and 2, have been determined. Kinetic studies indicated that compounds 1 and 2 show a mixed-type inhibition against TcAChE, with Ki values of 11.12 +/- 2.88 and 29.86 +/- 1.12 nM, respectively. The DNP rigidification results in a likely entropy-enthalpy compensation with solvation effects contributing primarily to AChE binding affinity. Molecular docking evidenced the molecular basis for the binding of compounds 1 and 2 to the active site of beta-secretase-1. Overall, these simplified DNP derivatives may represent new structural templates for the design of lead compounds for a more effective therapeutic strategy against AD by foreseeing a dual AChE and BACE-1 inhibitory activity. | ||
| - | + | Kinetic and structural studies on the interactions of Torpedo californica acetylcholinesterase with two donepezil-like rigid analogues.,Caliandro R, Pesaresi A, Cariati L, Procopio A, Oliverio M, Lamba D J Enzyme Inhib Med Chem. 2018 Dec;33(1):794-803. doi:, 10.1080/14756366.2018.1458030. PMID:29651884<ref>PMID:29651884</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5nap" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Acetylcholinesterase]] | ||
| + | [[Category: Tetronarce californica]] | ||
[[Category: Caliandro, R]] | [[Category: Caliandro, R]] | ||
[[Category: Lamba, D]] | [[Category: Lamba, D]] | ||
[[Category: Pesaresi, A]] | [[Category: Pesaresi, A]] | ||
| + | [[Category: Alzheimer's disease]] | ||
| + | [[Category: Donepezil analogue]] | ||
| + | [[Category: Green chemistry]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Inhibitor]] | ||
Revision as of 07:56, 2 May 2018
Torpedo californica acetylcholinesterase in complex with a non-chiral donepezil-like inhibitor 17
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