5k5e
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Discovery and Structure-Activity Relationships of a Highly Selective Butyrylcholinesterase Inhibitor by Structure-Based Virtual Screening== | |
| + | <StructureSection load='5k5e' size='340' side='right'caption='[[5k5e]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5k5e]] 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=5K5E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K5E 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]] 2.8Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6QS:[(2~{R})-OXOLAN-2-YL]METHYL+4-(9-ETHYLCARBAZOL-3-YL)-2-METHYL-5-OXIDANYLIDENE-4,6,7,8-TETRAHYDRO-1~{H}-QUINOLINE-3-CARBOXYLATE'>6QS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5k5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k5e OCA], [https://pdbe.org/5k5e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k5e RCSB], [https://www.ebi.ac.uk/pdbsum/5k5e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k5e 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 == | ||
| + | Structure-based virtual screening of two libraries containing 567981 molecules was used to discover novel, selective BuChE inhibitors, which are potentially superior symptomatic treatments in late-stage Alzheimer's disease. Compound 16 was identified as a highly selective submicromolar inhibitor of BuChE (huBuChE IC50 = 0.443 muM) with high permeability in the PAMPA-BBB model. The X-ray crystal structure of huBuChE in complex with 16 revealed the atomic-level interactions and offers opportunities for further development of the series. | ||
| - | + | Discovery and Structure-Activity Relationships of a Highly Selective Butyrylcholinesterase Inhibitor by Structure-Based Virtual Screening.,Dighe SN, Deora GS, De la Mora E, Nachon F, Chan S, Parat MO, Brazzolotto X, Ross BP J Med Chem. 2016 Jul 26. PMID:27405689<ref>PMID:27405689</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5k5e" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: De | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: | + | [[Category: Homo sapiens]] |
| + | [[Category: Large Structures]] | ||
| + | [[Category: Brazzolotto X]] | ||
| + | [[Category: De la Mora E]] | ||
| + | [[Category: Deora GS]] | ||
| + | [[Category: Dighe SN]] | ||
| + | [[Category: Nachon F]] | ||
| + | [[Category: Ross BP]] | ||
Current revision
Discovery and Structure-Activity Relationships of a Highly Selective Butyrylcholinesterase Inhibitor by Structure-Based Virtual Screening
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