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2hrq

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Revision as of 03:46, 10 September 2015

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

Structural highlights

2hrq is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Gene:	CES1 (HUMAN)
Activity:	Carboxylesterase, with EC number 3.1.1.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[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.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Brzezinski MR, Abraham TL, Stone CL, Dean RA, Bosron WF. Purification and characterization of a human liver cocaine carboxylesterase that catalyzes the production of benzoylecgonine and the formation of cocaethylene from alcohol and cocaine. Biochem Pharmacol. 1994 Nov 1;48(9):1747-55. PMID:7980644
↑ Pindel EV, Kedishvili NY, Abraham TL, Brzezinski MR, Zhang J, Dean RA, Bosron WF. Purification and cloning of a broad substrate specificity human liver carboxylesterase that catalyzes the hydrolysis of cocaine and heroin. J Biol Chem. 1997 Jun 6;272(23):14769-75. PMID:9169443
↑ Fleming CD, Edwards CC, Kirby SD, Maxwell DM, Potter PM, Cerasoli DM, Redinbo MR. Crystal structures of human carboxylesterase 1 in covalent complexes with the chemical warfare agents soman and tabun. Biochemistry. 2007 May 1;46(17):5063-71. Epub 2007 Apr 4. PMID:17407327 doi:10.1021/bi700246n

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2hrq"

@@ Line 2: / Line 2: @@
 <StructureSection load='2hrq' size='340' side='right' caption='[[2hrq]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2hrq]] 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=2HRQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HRQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2hrq]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HRQ FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CES1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CES1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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.rcsb.org/pdb/explore.do?structureId=2hrq RCSB], [http://www.ebi.ac.uk/pdbsum/2hrq PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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://pdbe.org/2hrq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hrq RCSB], [http://www.ebi.ac.uk/pdbsum/2hrq PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2hrq" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 36: / Line 37: @@
 </StructureSection>
 [[Category: Carboxylesterase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Fleming, C D]]
 [[Category: Redinbo, M R]]
 [[Category: Hydrolase]]
 [[Category: Soman]]

2hrq

From Proteopedia

Revision as of 03:46, 10 September 2015

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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