6ep4: Difference between revisions

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-'''Unreleased structure'''
-The entry 6ep4 is ON HOLD  until Paper Publication
+==Human butyrylcholinesterase in complex with decamethonium==
+<StructureSection load='6ep4' size='340' side='right'caption='[[6ep4]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6ep4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EP4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6EP4 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DME:DECAMETHONIUM+ION'>DME</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BCHE, CHE1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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://proteopedia.org/fgij/fg.htm?mol=6ep4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ep4 OCA], [http://pdbe.org/6ep4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ep4 RCSB], [http://www.ebi.ac.uk/pdbsum/6ep4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ep4 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 ==
+Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) hydrolyze the neurotransmitter acetylcholine and, thereby, function as coregulators of cholinergic neurotransmission. Although closely related, these enzymes display very different substrate specificities that only partially overlap. This disparity is largely due to differences in the number of aromatic residues lining the active site gorge, which leads to large differences in the shape of the gorge and potentially to distinct interactions with an individual ligand. Considerable structural information is available for the binding of a wide diversity of ligands to AChE. In contrast, structural data on the binding of reversible ligands to BChE are lacking. In a recent effort, an inhibitor competition approach was used to probe the overlap of ligand binding sites in BChE. Here, we extend this study by solving the crystal structures of human BChE in complex with five reversible ligands, namely, decamethonium, thioflavin T, propidium, huprine, and ethopropazine. We compare these structures to equivalent AChE complexes when available in the protein data bank and supplement this comparison with kinetic data and observations from isothermal titration calorimetry. This new information now allows us to define the binding mode of various ligand families and will be of importance in designing specific reversible ligands of BChE that behave as inhibitors or reactivators.
-Authors: Nachon, F., Brazzolotto, X., Wandhammer, M., Trovaslet-Leroy, M., Rosenberry, T.L., Macdonald, I.R., Darvesh, S.
+Comparison of the Binding of Reversible Inhibitors to Human Butyrylcholinesterase and Acetylcholinesterase: A Crystallographic, Kinetic and Calorimetric Study.,Rosenberry TL, Brazzolotto X, Macdonald IR, Wandhammer M, Trovaslet-Leroy M, Darvesh S, Nachon F Molecules. 2017 Nov 29;22(12). pii: molecules22122098. doi:, 10.3390/molecules22122098. PMID:29186056<ref>PMID:29186056</ref>
-Description: Human butyrylcholinesterase in complex with decamethonium
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Rosenberry, T.L]]
+<div class="pdbe-citations 6ep4" style="background-color:#fffaf0;"></div>
-[[Category: Wandhammer, M]]
+== References ==
-[[Category: Trovaslet-Leroy, M]]
+<references/>
-[[Category: Nachon, F]]
+__TOC__
+</StructureSection>
+[[Category: Cholinesterase]]
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Brazzolotto, X]]
 [[Category: Darvesh, S]]
-[[Category: Macdonald, I.R]]
+[[Category: Macdonald, I R]]
+[[Category: Nachon, F]]
+[[Category: Rosenberry, T L]]
+[[Category: Trovaslet-Leroy, M]]
+[[Category: Wandhammer, M]]
+[[Category: Complex]]
+[[Category: Hydrolase]]
+[[Category: Inhibitor]]
+[[Category: Quaternary ammonium]]