5nap: Difference between revisions
New page: '''Unreleased structure''' The entry 5nap is ON HOLD until Feb 28 2019 Authors: Caliandro, R., Pesaresi, A., Lamba, D. Description: Torpedo californica acetylcholinesterase in complex ... |
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==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 [https://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 [https://proteopedia.org/fgij/fg.htm?mol=5NAP 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]] 2.17Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5nap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nap OCA], [https://pdbe.org/5nap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nap RCSB], [https://www.ebi.ac.uk/pdbsum/5nap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nap ProSAT]</span></td></tr> | |||
</table> | |||
== 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;"> | |||
== 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> | ||
[[Category: Caliandro | <div class="pdbe-citations 5nap" style="background-color:#fffaf0;"></div> | ||
[[Category: Lamba | |||
[[Category: Pesaresi | ==See Also== | ||
*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Tetronarce californica]] | |||
[[Category: Caliandro R]] | |||
[[Category: Lamba D]] | |||
[[Category: Pesaresi A]] | |||
Latest revision as of 15:43, 15 November 2023
Torpedo californica acetylcholinesterase in complex with a non-chiral donepezil-like inhibitor 17Torpedo californica acetylcholinesterase in complex with a non-chiral donepezil-like inhibitor 17
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 PubMedAcetylcholinesterase 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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