5lkr
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Human Butyrylcholinesterase complexed with N-Propargyliperidines== | |
| + | <StructureSection load='5lkr' size='340' side='right' caption='[[5lkr]], [[Resolution|resolution]] 2.52Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5lkr]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LKR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LKR FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6YC:~{N}-(2-METHOXYETHYL)-~{N}-[[(3~{S})-1-PROP-2-YNYLPIPERIDIN-3-YL]METHYL]NAPHTHALENE-2-CARBOXAMIDE'>6YC</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cholinesterase Cholinesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.8 3.1.1.8] </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=5lkr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lkr OCA], [http://pdbe.org/5lkr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lkr RCSB], [http://www.ebi.ac.uk/pdbsum/5lkr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lkr ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/CHLE_HUMAN CHLE_HUMAN]] Defects in BCHE are the cause of butyrylcholinesterase deficiency (BChE deficiency) [MIM:[http://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 == | ||
| + | [[http://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 == | ||
| + | In the brains of patients with Alzheimer's disease, the enzymatic activities of butyrylcholinesterase (BChE) and monoamine oxidase B (MAO-B) are increased. While BChE is a viable therapeutic target for alleviation of symptoms caused by cholinergic hypofunction, MAO-B is a potential therapeutic target for prevention of neurodegeneration in Alzheimer's disease. Starting with piperidine-based selective human (h)BChE inhibitors and propargylamine-based MAO inhibitors, we have designed, synthesized and biochemically evaluated a series of N-propargylpiperidines. All of these compounds inhibited hBChE with good selectivity over the related enzyme, acetylcholinesterase, and crossed the blood-brain barrier in a parallel artificial membrane permeation assay. The crystal structure of one of the inhibitors (compound 3) in complex with hBChE revealed its binding mode. Three compounds (4, 5, 6) showed concomitant inhibition of MAO-B. Additionally, the most potent hBChE inhibitor 7 and dual BChE and MAO-B inhibitor 6 were non-cytotoxic and protected neuronal SH-SY5Y cells from toxic amyloid beta-peptide species. | ||
| - | + | N-Propargylpiperidines with naphthalene-2-carboxamide or naphthalene-2-sulfonamide moieties: Potential multifunctional anti-Alzheimer's agents.,Kosak U, Knez D, Coquelle N, Brus B, Pislar A, Nachon F, Brazzolotto X, Kos J, Colletier JP, Gobec S Bioorg Med Chem. 2016 Nov 19. pii: S0968-0896(16)30909-9. doi:, 10.1016/j.bmc.2016.11.032. PMID:27908752<ref>PMID:27908752</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5lkr" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Cholinesterase]] | ||
| + | [[Category: Colletier, J P]] | ||
[[Category: Coquelle, N]] | [[Category: Coquelle, N]] | ||
[[Category: Gobec, S]] | [[Category: Gobec, S]] | ||
[[Category: Knez, D]] | [[Category: Knez, D]] | ||
| - | [[Category: | + | [[Category: Alzheimer disease ad butyrylcholinesterase n-propargyliperidine]] |
| + | [[Category: Hydrolase]] | ||
Revision as of 19:08, 15 December 2016
Human Butyrylcholinesterase complexed with N-Propargyliperidines
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