1ya8: Difference between revisions

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-{{Seed}}
-[[Image:1ya8.png|left|200px]]
-<!--
+==Crystal Structure of Human Liver Carboxylesterase in complex with cleavage products of Mevastatin==
-The line below this paragraph, containing "STRUCTURE_1ya8", creates the "Structure Box" on the page.
+<StructureSection load='1ya8' size='340' side='right'caption='[[1ya8]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1ya8]] is a 3 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=1YA8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YA8 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MVB:(1S,7S,8S,8AR)-1,2,3,7,8,8A-HEXAHYDRO-7-METHYL-8-[2-[(2R,4R)-TETRAHYDRO-4-HY+DROXY-6-OXO-2H-PYRAN-2-YL]ETHYL]-1-NAPHTHALENOL'>MVB</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene>, <scene name='pdbligand=SMB:2-METHYLBUTANOIC+ACID'>SMB</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-{{STRUCTURE_1ya8|  PDB=1ya8  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ya8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ya8 OCA], [https://pdbe.org/1ya8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ya8 RCSB], [https://www.ebi.ac.uk/pdbsum/1ya8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ya8 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/ya/1ya8_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=1ya8 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Human carboxylesterase 1 (hCE1) exhibits broad substrate specificity and is involved in xenobiotic processing and endobiotic metabolism. We present and analyze crystal structures of hCE1 in complexes with the cholesterol-lowering drug mevastatin, the breast cancer drug tamoxifen, the fatty acyl ethyl ester (FAEE) analogue ethyl acetate, and the novel hCE1 inhibitor benzil. We find that mevastatin does not appear to be a substrate for hCE1, and instead acts as a partially non-competitive inhibitor of the enzyme. Similarly, we show that tamoxifen is a low micromolar, partially non-competitive inhibitor of hCE1. Further, we describe the structural basis for the inhibition of hCE1 by the nanomolar-affinity dione benzil, which acts by forming both covalent and non-covalent complexes with the enzyme. Our results provide detailed insights into the catalytic and non-catalytic processing of small molecules by hCE1, and suggest that the efficacy of clinical drugs may be modulated by targeted hCE1 inhibitors.
-===Crystal Structure of Human Liver Carboxylesterase in complex with cleavage products of Mevastatin===
+Structural insights into drug processing by human carboxylesterase 1: tamoxifen, mevastatin, and inhibition by benzil.,Fleming CD, Bencharit S, Edwards CC, Hyatt JL, Tsurkan L, Bai F, Fraga C, Morton CL, Howard-Williams EL, Potter PM, Redinbo MR J Mol Biol. 2005 Sep 9;352(1):165-77. PMID:16081098<ref>PMID:16081098</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1ya8" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_16081098}}, adds the Publication Abstract to the page
+*[[Carboxylesterase 3D structures|Carboxylesterase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 16081098 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_16081098}}
+__TOC__
+</StructureSection>
-==About this Structure==
-YA8 is a [[Single protein]] structure of 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=1YA8 OCA].
-==Reference==
-Structural insights into drug processing by human carboxylesterase 1: tamoxifen, mevastatin, and inhibition by benzil., Fleming CD, Bencharit S, Edwards CC, Hyatt JL, Tsurkan L, Bai F, Fraga C, Morton CL, Howard-Williams EL, Potter PM, Redinbo MR, J Mol Biol. 2005 Sep 9;352(1):165-77. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16081098 16081098]
-[[Category: Carboxylesterase]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Bencharit, S.]]
+[[Category: Bencharit S]]
-[[Category: Edwards, C C.]]
+[[Category: Edwards CC]]
-[[Category: Fleming, C D.]]
+[[Category: Fleming CD]]
-[[Category: Howard-Williams, E L.]]
+[[Category: Howard-Williams EL]]
-[[Category: Hyatt, J L.]]
+[[Category: Hyatt JL]]
-[[Category: Morton, C L.]]
+[[Category: Morton CL]]
-[[Category: Potter, P M.]]
+[[Category: Potter PM]]
-[[Category: Redinbo, M R.]]
+[[Category: Redinbo MR]]
-[[Category: Carboxylesterase]]
-[[Category: Hydrolase]]
-[[Category: Mevastatin]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 05:36:08 2008''