View source for 7aiy


==Crystal structure of human butyrylcholinesterase in complex with 2-{1-[4-(12-Amino-3-chloro-6,7,10,11-tetrahydro-7,11-methanocycloocta[b]quinolin-9-yl)butyl]-1H-1,2,3-triazol-4-yl}-N-[4-hydroxy-3-methoxybenzyl]acetamide==
<StructureSection load='7aiy' size='340' side='right'caption='[[7aiy]], [[Resolution|resolution]] 2.94&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7aiy]] 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=7AIY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AIY 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]] 2.937&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8U2:2-{1-[4-(12-Amino-3-chloro-6,7,10,11-tetrahydro-7,11-methanocycloocta[b]quinolin-9-yl)butyl]-1H-1,2,3-triazol-4-yl}-N-[4-hydroxy-3-methoxybenzyl]acetamide'>8U2</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=7aiy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aiy OCA], [https://pdbe.org/7aiy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aiy RCSB], [https://www.ebi.ac.uk/pdbsum/7aiy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aiy ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CHLE_HUMAN CHLE_HUMAN] Defects in BCHE are the cause of butyrylcholinesterase deficiency (BChE deficiency) [MIM:[https://omim.org/entry/177400 177400]. BChE deficiency is a metabolic disorder characterized by prolonged apnoea after the use of certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium and other ester local anesthetics. The duration of the prolonged apnoea varies significantly depending on the extent of the enzyme deficiency. BChE deficiency is a multifactorial disorder. The hereditary condition is transmitted as an autosomal recessive trait.
== Function ==
[https://www.uniprot.org/uniprot/CHLE_HUMAN CHLE_HUMAN] Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.<ref>PMID:19542320</ref> <ref>PMID:19452557</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The combination of the scaffolds of the cholinesterase inhibitor huprine Y and the antioxidant capsaicin results in compounds with nanomolar potencies toward human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) that retain or improve the antioxidant properties of capsaicin. Crystal structures of their complexes with AChE and BChE revealed the molecular basis for their high potency. Brain penetration was confirmed by biodistribution studies in C57BL6 mice, with one compound (5i) displaying better brain/plasma ratio than donepezil. Chronic treatment of 10 month-old APP/PS1 mice with 5i (2 mg/kg, i.p., 3 times per week, 4 weeks) rescued learning and memory impairments, as measured by three different behavioral tests, delayed the Alzheimer-like pathology progression, as suggested by a significantly reduced Abeta42/Abeta40 ratio in the hippocampus, improved basal synaptic efficacy, and significantly reduced hippocampal oxidative stress and neuroinflammation. Compound 5i emerges as an interesting anti-Alzheimer lead with beneficial effects on cognitive symptoms and on some underlying disease mechanisms.

Discovery of a Potent Dual Inhibitor of Acetylcholinesterase and Butyrylcholinesterase with Antioxidant Activity that Alleviates Alzheimer-like Pathology in Old APP/PS1 Mice.,Viayna E, Coquelle N, Cieslikiewicz-Bouet M, Cisternas P, Oliva CA, Sanchez-Lopez E, Ettcheto M, Bartolini M, De Simone A, Ricchini M, Rendina M, Pons M, Firuzi O, Perez B, Saso L, Andrisano V, Nachon F, Brazzolotto X, Garcia ML, Camins A, Silman I, Jean L, Inestrosa NC, Colletier JP, Renard PY, Munoz-Torrero D J Med Chem. 2021 Jan 14;64(1):812-839. doi: 10.1021/acs.jmedchem.0c01775. Epub, 2020 Dec 28. PMID:33356266<ref>PMID:33356266</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7aiy" style="background-color:#fffaf0;"></div>

==See Also==
*[[Butyrylcholinesterase 3D structures|Butyrylcholinesterase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Colletier JP]]
[[Category: Coquelle N]]