3i2g: Difference between revisions
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==Cocaine Esterase with mutation G173Q, bound to DTT adduct== | ==Cocaine Esterase with mutation G173Q, bound to DTT adduct== | ||
<StructureSection load='3i2g' size='340' side='right' caption='[[3i2g]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='3i2g' size='340' side='right' caption='[[3i2g]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3i2g]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3i2g]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Rhosm Rhosm]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I2G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3I2G FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DBC:(4S,5S)-4,5-BIS(MERCAPTOMETHYL)-1,3-DIOXOLAN-2-OL'>DBC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DBC:(4S,5S)-4,5-BIS(MERCAPTOMETHYL)-1,3-DIOXOLAN-2-OL'>DBC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ju3|1ju3]], [[1ju4|1ju4]], [[1l7r|1l7r]], [[1l7q|1l7q]], [[3i2f|3i2f]], [[3i2h|3i2h]], [[3i2i|3i2i]], [[3i2j|3i2j]], [[3i2k|3i2k]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ju3|1ju3]], [[1ju4|1ju4]], [[1l7r|1l7r]], [[1l7q|1l7q]], [[3i2f|3i2f]], [[3i2h|3i2h]], [[3i2i|3i2i]], [[3i2j|3i2j]], [[3i2k|3i2k]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cocaine Esterase, cocE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=104109 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cocaine Esterase, cocE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=104109 RHOSM])</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=3i2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i2g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3i2g RCSB], [http://www.ebi.ac.uk/pdbsum/3i2g 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=3i2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i2g OCA], [http://pdbe.org/3i2g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3i2g RCSB], [http://www.ebi.ac.uk/pdbsum/3i2g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3i2g ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | </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=3i2g ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3i2g" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Rhosm]] | ||
[[Category: Nance, M R]] | [[Category: Nance, M R]] | ||
[[Category: Tesmer, J J.G]] | [[Category: Tesmer, J J.G]] | ||
[[Category: Alpha/beta hydrolase]] | [[Category: Alpha/beta hydrolase]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
Revision as of 19:02, 4 August 2016
Cocaine Esterase with mutation G173Q, bound to DTT adductCocaine Esterase with mutation G173Q, bound to DTT adduct
Structural highlights
Function[COCE_RHOSM] Hydrolyzes cocaine to benzoate and ecgonine methyl ester, endowing the bacteria with the ability to utilize cocaine as a sole source of carbon and energy for growth, as this bacterium lives in the rhizosphere of coca plants. Also efficiently hydrolyzes cocaethylene, a more potent cocaine metabolite that has been observed in patients who concurrently abuse cocaine and alcohol. Is able to prevent cocaine-induced convulsions and lethality in rat.[1] [2] [3] 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 PubMedCocaine is considered to be the most addictive of all substances of abuse and mediates its effects by inhibiting monoamine transporters, primarily the dopamine transporters. There are currently no small molecules that can be used to combat its toxic and addictive properties, in part because of the difficulty of developing compounds that inhibit cocaine binding without having intrinsic effects on dopamine transport. Most of the effective cocaine inhibitors also display addictive properties. We have recently reported the use of cocaine esterase (CocE) to accelerate the removal of systemic cocaine and to prevent cocaine-induced lethality. However, wild-type CocE is relatively unstable at physiological temperatures (tau(1/2) approximately 13 min at 37 degrees C), presenting challenges for its development as a viable therapeutic agent. We applied computational approaches to predict mutations to stabilize CocE and showed that several of these have increased stability both in vitro and in vivo, with the most efficacious mutant (T172R/G173Q) extending half-life up to 370 min. Here we present novel X-ray crystallographic data on these mutants that provide a plausible model for the observed enhanced stability. We also more extensively characterize the previously reported variants and report on a new stabilizing mutant, L169K. The improved stability of these engineered CocE enzymes will have a profound influence on the use of this protein to combat cocaine-induced toxicity and addiction in humans. Structural analysis of thermostabilizing mutations of cocaine esterase.,Narasimhan D, Nance MR, Gao D, Ko MC, Macdonald J, Tamburi P, Yoon D, Landry DM, Woods JH, Zhan CG, Tesmer JJ, Sunahara RK Protein Eng Des Sel. 2010 Jul;23(7):537-47. Epub 2010 Apr 30. PMID:20436035[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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