6r6v
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of recombinant human butyrylcholinesterase in complex with a fluorescent coumarin-based probe== | |
| + | <StructureSection load='6r6v' size='340' side='right'caption='[[6r6v]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6r6v]] is a 1 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=6R6V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R6V 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]] 2.5Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=JU5:~{N}-[[(3~{S})-1-[[2-[7-(diethylamino)-2-oxidanylidene-chromen-3-yl]-1,3-thiazol-4-yl]methyl]piperidin-3-yl]methyl]-~{N}-[2-(dimethylamino)ethyl]naphthalene-2-carboxamide'>JU5</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6r6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r6v OCA], [https://pdbe.org/6r6v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r6v RCSB], [https://www.ebi.ac.uk/pdbsum/6r6v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r6v 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 == | ||
| + | Brain butyrylcholinesterase (BChE) is an attractive target for drugs designed for the treatment of Alzheimer's disease (AD) in its advanced stages. It also potentially represents a biomarker for progression of this disease. Based on the crystal structure of previously described highly potent, reversible, and selective BChE inhibitors, we have developed the fluorescent probes that are selective towards human BChE. The most promising probes also maintain their inhibition of BChE in the low nanomolar range with high selectivity over acetylcholinesterase. Kinetic studies of probes reveal a reversible mixed inhibition mechanism, with binding of these fluorescent probes to both the free and acylated enzyme. Probes show environment-sensitive emission, and additionally, one of them also shows significant enhancement of fluorescence intensity upon binding to the active site of BChE. Finally, the crystal structures of probes in complex with human BChE are reported, which offer an excellent base for further development of this library of compounds. | ||
| - | + | Development of potent reversible selective inhibitors of butyrylcholinesterase as fluorescent probes.,Pajk S, Knez D, Kosak U, Zorovic M, Brazzolotto X, Coquelle N, Nachon F, Colletier JP, Zivin M, Stojan J, Gobec S J Enzyme Inhib Med Chem. 2020 Dec;35(1):498-505. doi:, 10.1080/14756366.2019.1710502. PMID:31914836<ref>PMID:31914836</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6r6v" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: | + | *[[Butyrylcholinesterase 3D structures|Butyrylcholinesterase 3D structures]] |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Brazzolotto X]] | ||
| + | [[Category: Gobec S]] | ||
| + | [[Category: Knez D]] | ||
| + | [[Category: Nachon F]] | ||
Current revision
Structure of recombinant human butyrylcholinesterase in complex with a fluorescent coumarin-based probe
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