1mx1: Difference between revisions

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-[[Image:1mx1.png|left|200px]]
-{{STRUCTURE_1mx1|  PDB=1mx1  |  SCENE=  }}
+==Crystal Structure of Human Liver Carboxylesterase in complex with tacrine==
+<StructureSection load='1mx1' size='340' side='right'caption='[[1mx1]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1mx1]] is a 6 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=1MX1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MX1 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]] 2.4&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene>, <scene name='pdbligand=THA:TACRINE'>THA</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=1mx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mx1 OCA], [https://pdbe.org/1mx1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mx1 RCSB], [https://www.ebi.ac.uk/pdbsum/1mx1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mx1 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/EST1_HUMAN EST1_HUMAN] Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate.<ref>PMID:7980644</ref> <ref>PMID:9169443</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/mx/1mx1_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1mx1 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Human carboxylesterase 1 (hCE1) is a broad-spectrum bioscavenger that plays important roles in narcotic metabolism, clinical prodrug activation, and the processing of fatty acid and cholesterol derivatives. We determined the 2.4 A crystal structure of hCE1 in complex with tacrine, the first drug approved for treating Alzheimer's disease, and compare this structure to the Torpedo californica acetylcholinesterase (AcChE)-tacrine complex. Tacrine binds in multiple orientations within the catalytic gorge of hCE1, while it stacks in the smaller AcChE active site between aromatic side chains. Our results show that hCE1's promiscuous action on distinct substrates is enhanced by its ability to interact with ligands in multiple orientations at once. Further, we use our structure to identify tacrine derivatives that act as low-micromolar inhibitors of hCE1 and may provide new avenues for treating narcotic abuse and cholesterol-related diseases.
-===Crystal Structure of Human Liver Carboxylesterase in complex with tacrine===
+Crystal structure of human carboxylesterase 1 complexed with the Alzheimer's drug tacrine: from binding promiscuity to selective inhibition.,Bencharit S, Morton CL, Hyatt JL, Kuhn P, Danks MK, Potter PM, Redinbo MR Chem Biol. 2003 Apr;10(4):341-9. PMID:12725862<ref>PMID:12725862</ref>
-{{ABSTRACT_PUBMED_12725862}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 1mx1" style="background-color:#fffaf0;"></div>
-[[1mx1]] is a 6 chain structure 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=1MX1 OCA].
 ==See Also==
-*[[Carboxylesterase|Carboxylesterase]]
+*[[Carboxylesterase 3D structures|Carboxylesterase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:012725862</ref><references group="xtra"/>
+__TOC__
-[[Category: Carboxylesterase]]
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Bencharit, S.]]
+[[Category: Large Structures]]
-[[Category: Danks, M K.]]
+[[Category: Bencharit S]]
-[[Category: Hyatt, J L.]]
+[[Category: Danks MK]]
-[[Category: Kuhn, P.]]
+[[Category: Hyatt JL]]
-[[Category: Morton, C L.]]
+[[Category: Kuhn P]]
-[[Category: Potter, P M.]]
+[[Category: Morton CL]]
-[[Category: Redinbo, M R.]]
+[[Category: Potter PM]]
-[[Category: Esterase]]
+[[Category: Redinbo MR]]
-[[Category: Esterase inhibitor]]
-[[Category: Hydrolase]]