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| | ==Comparison of the structure and activity of glycosylated and aglycosylated Human Carboxylesterase 1== | | ==Comparison of the structure and activity of glycosylated and aglycosylated Human Carboxylesterase 1== |
| - | <StructureSection load='5a7g' size='340' side='right' caption='[[5a7g]], [[Resolution|resolution]] 1.48Å' scene=''> | + | <StructureSection load='5a7g' size='340' side='right'caption='[[5a7g]], [[Resolution|resolution]] 1.48Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5a7g]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5A7G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5A7G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5a7g]] is a 1 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=5A7G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5A7G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.48Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5a7f|5a7f]], [[5a7h|5a7h]]</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></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=5a7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5a7g OCA], [http://pdbe.org/5a7g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5a7g RCSB], [http://www.ebi.ac.uk/pdbsum/5a7g PDBsum]</span></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=5a7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5a7g OCA], [https://pdbe.org/5a7g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5a7g RCSB], [https://www.ebi.ac.uk/pdbsum/5a7g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5a7g ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5a7g" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5a7g" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Carboxylesterase 3D structures|Carboxylesterase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Charlton, M]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Owen, R J]] | + | [[Category: Large Structures]] |
| - | [[Category: Scott, D J]] | + | [[Category: Arena de Souza V]] |
| - | [[Category: Souza, V Arena de]] | + | [[Category: Charlton M]] |
| - | [[Category: Walsh, M A]] | + | [[Category: Owen RJ]] |
| - | [[Category: Esterase]] | + | [[Category: Scott DJ]] |
| - | [[Category: Hydrolase]] | + | [[Category: Walsh MA]] |
| Structural highlights
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]
Publication Abstract from PubMed
Human Carboxylesterase 1 (hCES1) is the key liver microsomal enzyme responsible for detoxification and metabolism of a variety of clinical drugs. To analyse the role of the single N-linked glycan on the structure and activity of the enzyme, authentically glycosylated and aglycosylated hCES1, generated by mutating asparagine 79 to glutamine, were produced in human embryonic kidney cells. Purified enzymes were shown to be predominantly trimeric in solution by analytical ultracentrifugation. The purified aglycosylated enzyme was found to be more active than glycosylated hCES1 and analysis of enzyme kinetics revealed that both enzymes exhibit positive cooperativity. Crystal structures of hCES1 a catalytically inactive mutant (S221A) and the aglycosylated enzyme were determined in the absence of any ligand or substrate to high resolutions (1.86 A, 1.48 A and 2.01 A, respectively). Superposition of all three structures showed only minor conformational differences with a root mean square deviations of around 0.5 A over all Calpha positions. Comparison of the active sites of these un-liganded enzymes with the structures of hCES1-ligand complexes showed that side-chains of the catalytic triad were pre-disposed for substrate binding. Overall the results indicate that preventing N-glycosylation of hCES1 does not significantly affect the structure or activity of the enzyme.
Comparison of the Structure and Activity of Glycosylated and Aglycosylated Human Carboxylesterase 1.,Arena de Souza V, Scott DJ, Nettleship JE, Rahman N, Charlton MH, Walsh MA, Owens RJ PLoS One. 2015 Dec 11;10(12):e0143919. doi: 10.1371/journal.pone.0143919., eCollection 2015. PMID:26657071[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Arena de Souza V, Scott DJ, Nettleship JE, Rahman N, Charlton MH, Walsh MA, Owens RJ. Comparison of the Structure and Activity of Glycosylated and Aglycosylated Human Carboxylesterase 1. PLoS One. 2015 Dec 11;10(12):e0143919. doi: 10.1371/journal.pone.0143919., eCollection 2015. PMID:26657071 doi:http://dx.doi.org/10.1371/journal.pone.0143919
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