2hrq

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[[Image:2hrq.jpg|left|200px]]
 
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{{Structure
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==Crystal structure of Human Liver Carboxylesterase 1 (hCE1) in covalent complex with the nerve agent Soman (GD)==
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|PDB= 2hrq |SIZE=350|CAPTION= <scene name='initialview01'>2hrq</scene>, resolution 2.70&Aring;
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<StructureSection load='2hrq' size='340' side='right'caption='[[2hrq]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=GD7:(1R)-1,2,2-TRIMETHYLPROPYL+(R)-METHYLPHOSPHINATE'>GD7</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>, <scene name='pdbligand=SUC:SUCROSE'>SUC</scene>
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<table><tr><td colspan='2'>[[2hrq]] 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=2HRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HRQ FirstGlance]. <br>
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydrolase Hydrolase], 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]] 2.7&#8491;</td></tr>
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|GENE= CES1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GD7:(1R)-1,2,2-TRIMETHYLPROPYL+(R)-METHYLPHOSPHINATE'>GD7</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PRD_900003:sucrose'>PRD_900003</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=2hrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hrq OCA], [https://pdbe.org/2hrq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hrq RCSB], [https://www.ebi.ac.uk/pdbsum/2hrq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hrq ProSAT]</span></td></tr>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hrq OCA], [http://www.ebi.ac.uk/pdbsum/2hrq PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2hrq 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/hr/2hrq_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2hrq 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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The organophosphorus nerve agents sarin, soman, tabun, and VX exert their toxic effects by inhibiting the action of human acetylcholinesterase, a member of the serine hydrolase superfamily of enzymes. The current treatments for nerve agent exposure must be administered quickly to be effective, and they often do not eliminate long-term toxic side effects associated with organophosphate poisoning. Thus, there is significant need for effective prophylactic methods to protect at-risk personnel from nerve agent exposure, and protein-based approaches have emerged as promising candidates. We present the 2.7 A resolution crystal structures of the serine hydrolase human carboxylesterase 1 (hCE1), a broad-spectrum drug metabolism enzyme, in covalent acyl-enzyme intermediate complexes with the chemical weapons soman and tabun. The structures reveal that hCE1 binds stereoselectively to these nerve agents; for example, hCE1 appears to react preferentially with the 10(4)-fold more lethal PS stereoisomer of soman relative to the PR form. In addition, structural features of the hCE1 active site indicate that the enzyme may be resistant to dead-end organophosphate aging reactions that permanently inactivate other serine hydrolases. Taken together, these data provide important structural details toward the goal of engineering hCE1 into an organophosphate hydrolase and protein-based therapeutic for nerve agent exposure.
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'''Crystal structure of Human Liver Carboxylesterase 1 (hCE1) in covalent complex with the nerve agent Soman (GD)'''
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Crystal structures of human carboxylesterase 1 in covalent complexes with the chemical warfare agents soman and tabun.,Fleming CD, Edwards CC, Kirby SD, Maxwell DM, Potter PM, Cerasoli DM, Redinbo MR Biochemistry. 2007 May 1;46(17):5063-71. Epub 2007 Apr 4. PMID:17407327<ref>PMID:17407327</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 2hrq" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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The organophosphorus nerve agents sarin, soman, tabun, and VX exert their toxic effects by inhibiting the action of human acetylcholinesterase, a member of the serine hydrolase superfamily of enzymes. The current treatments for nerve agent exposure must be administered quickly to be effective, and they often do not eliminate long-term toxic side effects associated with organophosphate poisoning. Thus, there is significant need for effective prophylactic methods to protect at-risk personnel from nerve agent exposure, and protein-based approaches have emerged as promising candidates. We present the 2.7 A resolution crystal structures of the serine hydrolase human carboxylesterase 1 (hCE1), a broad-spectrum drug metabolism enzyme, in covalent acyl-enzyme intermediate complexes with the chemical weapons soman and tabun. The structures reveal that hCE1 binds stereoselectively to these nerve agents; for example, hCE1 appears to react preferentially with the 10(4)-fold more lethal PS stereoisomer of soman relative to the PR form. In addition, structural features of the hCE1 active site indicate that the enzyme may be resistant to dead-end organophosphate aging reactions that permanently inactivate other serine hydrolases. Taken together, these data provide important structural details toward the goal of engineering hCE1 into an organophosphate hydrolase and protein-based therapeutic for nerve agent exposure.
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*[[Carboxylesterase 3D structures|Carboxylesterase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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2HRQ 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=2HRQ OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Crystal structures of human carboxylesterase 1 in covalent complexes with the chemical warfare agents soman and tabun., Fleming CD, Edwards CC, Kirby SD, Maxwell DM, Potter PM, Cerasoli DM, Redinbo MR, Biochemistry. 2007 May 1;46(17):5063-71. Epub 2007 Apr 4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17407327 17407327]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Hydrolase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Fleming CD]]
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[[Category: Fleming, C D.]]
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[[Category: Redinbo MR]]
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[[Category: Redinbo, M R.]]
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[[Category: carboxylesterase]]
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[[Category: hydrolase]]
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[[Category: soman]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:34:30 2008''
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Current revision

Crystal structure of Human Liver Carboxylesterase 1 (hCE1) in covalent complex with the nerve agent Soman (GD)

PDB ID 2hrq

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