2h7c

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[[Image:2h7c.gif|left|200px]]
 
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{{Structure
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==Crystal structure of human carboxylesterase in complex with Coenzyme A==
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|PDB= 2h7c |SIZE=350|CAPTION= <scene name='initialview01'>2h7c</scene>, resolution 2.00&Aring;
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<StructureSection load='2h7c' size='340' side='right'caption='[[2h7c]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <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=SO4:SULFATE+ION'>SO4</scene>
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<table><tr><td colspan='2'>[[2h7c]] 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=2H7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H7C FirstGlance]. <br>
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Carboxylesterase Carboxylesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.1 3.1.1.1] </span>
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</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&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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|DOMAIN=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2h7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h7c OCA], [https://pdbe.org/2h7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h7c RCSB], [https://www.ebi.ac.uk/pdbsum/2h7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h7c ProSAT]</span></td></tr>
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|RELATEDENTRY=[[1mx1|1MX1]], [[1mx5|1MX5]], [[1mx9|1MX9]], [[1ya4|1YA4]], [[1ya8|1YA8]], [[1yah|1YAH]], [[2dqy|2DQY]], [[2dqz|2DQZ]], [[2dr0|2DR0]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2h7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h7c OCA], [http://www.ebi.ac.uk/pdbsum/2h7c PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2h7c RCSB]</span>
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== Function ==
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}}
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h7/2h7c_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2h7c ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Human carboxylesterase 1 (hCE1) is a drug and endobiotic-processing serine hydrolase that exhibits relatively broad substrate specificity. It has been implicated in a variety of endogenous cholesterol metabolism pathways including the following apparently disparate reactions: cholesterol ester hydrolysis (CEH), fatty acyl Coenzyme A hydrolysis (FACoAH), acyl-Coenzyme A:cholesterol acyltransfer (ACAT), and fatty acyl ethyl ester synthesis (FAEES). The structural basis for the ability of hCE1 to perform these catalytic actions involving large substrates and products has remained unclear. Here we present four crystal structures of the hCE1 glycoprotein in complexes with the following endogenous substrates or substrate analogues: Coenzyme A, the fatty acid palmitate, and the bile acids cholate and taurocholate. While the active site of hCE1 was known to be promiscuous and capable of interacting with a variety of chemically distinct ligands, these structures reveal that the enzyme contains two additional ligand-binding sites and that each site also exhibits relatively non-specific ligand-binding properties. Using this multisite promiscuity, hCE1 appears structurally capable of assembling several catalytic events depending, apparently, on the physiological state of the cellular environment. These results expand our understanding of enzyme promiscuity and indicate that, in the case of hCE1, multiple non-specific sites are employed to perform distinct catalytic actions.
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'''Crystal structure of human carboxylesterase in complex with Coenzyme A'''
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Multisite promiscuity in the processing of endogenous substrates by human carboxylesterase 1.,Bencharit S, Edwards CC, Morton CL, Howard-Williams EL, Kuhn P, Potter PM, Redinbo MR J Mol Biol. 2006 Oct 13;363(1):201-14. Epub 2006 Aug 15. PMID:16962139<ref>PMID:16962139</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2h7c" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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Human carboxylesterase 1 (hCE1) is a drug and endobiotic-processing serine hydrolase that exhibits relatively broad substrate specificity. It has been implicated in a variety of endogenous cholesterol metabolism pathways including the following apparently disparate reactions: cholesterol ester hydrolysis (CEH), fatty acyl Coenzyme A hydrolysis (FACoAH), acyl-Coenzyme A:cholesterol acyltransfer (ACAT), and fatty acyl ethyl ester synthesis (FAEES). The structural basis for the ability of hCE1 to perform these catalytic actions involving large substrates and products has remained unclear. Here we present four crystal structures of the hCE1 glycoprotein in complexes with the following endogenous substrates or substrate analogues: Coenzyme A, the fatty acid palmitate, and the bile acids cholate and taurocholate. While the active site of hCE1 was known to be promiscuous and capable of interacting with a variety of chemically distinct ligands, these structures reveal that the enzyme contains two additional ligand-binding sites and that each site also exhibits relatively non-specific ligand-binding properties. Using this multisite promiscuity, hCE1 appears structurally capable of assembling several catalytic events depending, apparently, on the physiological state of the cellular environment. These results expand our understanding of enzyme promiscuity and indicate that, in the case of hCE1, multiple non-specific sites are employed to perform distinct catalytic actions.
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*[[Carboxylesterase|Carboxylesterase]]
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*[[Carboxylesterase 3D structures|Carboxylesterase 3D structures]]
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==About this Structure==
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== References ==
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2H7C 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=2H7C OCA].
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<references/>
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__TOC__
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==Reference==
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</StructureSection>
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Multisite promiscuity in the processing of endogenous substrates by human carboxylesterase 1., Bencharit S, Edwards CC, Morton CL, Howard-Williams EL, Kuhn P, Potter PM, Redinbo MR, J Mol Biol. 2006 Oct 13;363(1):201-14. Epub 2006 Aug 15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16962139 16962139]
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[[Category: Carboxylesterase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Bencharit, S.]]
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[[Category: Bencharit S]]
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[[Category: Edwards, C C.]]
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[[Category: Edwards CC]]
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[[Category: Howard-Williams, E L.]]
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[[Category: Howard-Williams EL]]
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[[Category: Morton, C L.]]
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[[Category: Morton CL]]
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[[Category: Potter, P M.]]
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[[Category: Potter PM]]
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[[Category: Redinbo, M R.]]
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[[Category: Redinbo MR]]
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[[Category: cholesteryl esterase]]
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[[Category: enzyme]]
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[[Category: esterase]]
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[[Category: hydrolase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:26:29 2008''
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Current revision

Crystal structure of human carboxylesterase in complex with Coenzyme A

PDB ID 2h7c

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