2j4c: Difference between revisions

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-[[Image:2j4c.png|left|200px]]
-{{STRUCTURE_2j4c|  PDB=2j4c  |  SCENE=  }}
+==Structure of human Butyrylcholinesterase in complex with 10mM HgCl2==
+<StructureSection load='2j4c' size='340' side='right'caption='[[2j4c]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2j4c]] 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=2J4C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J4C 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]] 2.75&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BUA:BUTANOIC+ACID'>BUA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CSS:S-MERCAPTOCYSTEINE'>CSS</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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=2j4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j4c OCA], [https://pdbe.org/2j4c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j4c RCSB], [https://www.ebi.ac.uk/pdbsum/2j4c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j4c 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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j4/2j4c_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2j4c ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The poorly known mechanism of inhibition of cholinesterases by inorganic mercury (HgCl2) has been studied with a view to using these enzymes as biomarkers or as biological components of biosensors to survey polluted areas. The inhibition of a variety of cholinesterases by HgCl2 was investigated by kinetic studies, X-ray crystallography, and dynamic light scattering. Our results show that when a free sensitive sulfhydryl group is present in the enzyme, as in Torpedo californica acetylcholinesterase, inhibition is irreversible and follows pseudo-first-order kinetics that are completed within 1 h in the micromolar range. When the free sulfhydryl group is not sensitive to mercury (Drosophila melanogaster acetylcholinesterase and human butyrylcholinesterase) or is otherwise absent (Electrophorus electricus acetylcholinesterase), then inhibition occurs in the millimolar range. Inhibition follows a slow binding model, with successive binding of two mercury ions to the enzyme surface. Binding of mercury ions has several consequences: reversible inhibition, enzyme denaturation, and protein aggregation, protecting the enzyme from denaturation. Mercury-induced inactivation of cholinesterases is thus a rather complex process. Our results indicate that among the various cholinesterases that we have studied, only Torpedo californica acetylcholinesterase is suitable for mercury detection using biosensors, and that a careful study of cholinesterase inhibition in a species is a prerequisite before using it as a biomarker to survey mercury in the environment.
-===STRUCTURE OF HUMAN BUTYRYLCHOLINESTERASE IN COMPLEX WITH 10MM HGCL2===
+Mechanisms of cholinesterase inhibition by inorganic mercury.,Frasco MF, Colletier JP, Weik M, Carvalho F, Guilhermino L, Stojan J, Fournier D FEBS J. 2007 Apr;274(7):1849-61. Epub 2007 Mar 12. PMID:17355286<ref>PMID:17355286</ref>
-{{ABSTRACT_PUBMED_17355286}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 2j4c" style="background-color:#fffaf0;"></div>
-[[2j4c]] is a 1 chain structure of [[Butyrylcholinesterase]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J4C OCA].
 ==See Also==
-*[[Butyrylcholinesterase|Butyrylcholinesterase]]
+*[[Butyrylcholinesterase 3D structures|Butyrylcholinesterase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:017355286</ref><references group="xtra"/>
+__TOC__
-[[Category: Cholinesterase]]
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Carvalho, F.]]
+[[Category: Large Structures]]
-[[Category: Colletier, J P.]]
+[[Category: Carvalho F]]
-[[Category: Fournier, D.]]
+[[Category: Colletier JP]]
-[[Category: Frasco, M F.]]
+[[Category: Fournier D]]
-[[Category: Guilhermino, L.]]
+[[Category: Frasco MF]]
-[[Category: Stojan, J.]]
+[[Category: Guilhermino L]]
-[[Category: Weik, M.]]
+[[Category: Stojan J]]
-[[Category: Cholinesterase]]
+[[Category: Weik M]]
-[[Category: Disease mutation]]
-[[Category: Glycoprotein]]
-[[Category: Hydrolase]]
-[[Category: Inhibition]]
-[[Category: Inorganic mercury]]
-[[Category: Serine esterase]]