3ida

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{{STRUCTURE_3ida| PDB=3ida | SCENE= }}
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==Thermostable Cocaine Esterase with mutations L169K and G173Q, bound to DTT adduct==
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===Thermostable Cocaine Esterase with mutations L169K and G173Q, bound to DTT adduct===
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<StructureSection load='3ida' size='340' side='right' caption='[[3ida]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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{{ABSTRACT_PUBMED_20086035}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3ida]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Rhodococcus_sp. Rhodococcus sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IDA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3IDA FirstGlance]. <br>
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</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></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3i2k|3i2k]], [[3i2j|3i2j]], [[3i2i|3i2i]], [[3i2g|3i2g]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cocE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1831 Rhodococcus sp.])</td></tr>
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<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=3ida FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ida OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ida RCSB], [http://www.ebi.ac.uk/pdbsum/3ida PDBsum]</span></td></tr>
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</table>
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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/id/3ida_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/chain_selection.php?pdb_ID=2ata 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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Rhodococcal cocaine esterase (CocE) is an attractive potential treatment for both cocaine overdose and cocaine addiction. CocE directly degrades cocaine into inactive products, whereas traditional small-molecule approaches require blockade of the inhibitory action of cocaine on a diverse array of monoamine transporters and ion channels. The usefulness of wild-type (wt) cocaine esterase is hampered by its inactivation at 37 degrees C. Herein, we characterize the most thermostable form of this enzyme to date, CocE-L169K/G173Q. In vitro kinetic analyses reveal that CocE-L169K/G173Q displays a half-life of 2.9 days at 37 degrees C, which represents a 340-fold improvement over wt and is 15-fold greater than previously reported mutants. Crystallographic analyses of CocE-L169K/G173Q, determined at 1.6-A resolution, suggest that stabilization involves enhanced domain-domain interactions involving van der Waals interactions and hydrogen bonding. In vivo rodent studies reveal that intravenous pretreatment with CocE-L169K/G173Q in mice provides protection from cocaine-induced lethality for longer time periods before cocaine administration than wt CocE. Furthermore, intravenous administration (pretreatment) of CocE-L169K/G173Q prevents self-administration of cocaine in a time-dependent manner. Termination of the in vivo effects of CoCE seems to be dependent on, but not proportional to, its clearance from plasma as its half-life is approximately 2.3 h and similar to that of wt CocE (2.2 h). Taken together these data suggest that CocE-L169K/G173Q possesses many of the properties of a biological therapeutic for treating cocaine abuse but requires additional development to improve its serum half-life.
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==About this Structure==
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A thermally stable form of bacterial cocaine esterase: a potential therapeutic agent for treatment of cocaine abuse.,Brim RL, Nance MR, Youngstrom DW, Narasimhan D, Zhan CG, Tesmer JJ, Sunahara RK, Woods JH Mol Pharmacol. 2010 Apr;77(4):593-600. Epub 2010 Jan 19. PMID:20086035<ref>PMID:20086035</ref>
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[[3ida]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Rhodococcus_sp. Rhodococcus sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IDA OCA].
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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>
==See Also==
==See Also==
*[[Cocaine esterase|Cocaine esterase]]
*[[Cocaine esterase|Cocaine esterase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:020086035</ref><references group="xtra"/>
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__TOC__
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[[Category: Rhodococcus sp.]]
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</StructureSection>
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[[Category: Nance, M R.]]
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[[Category: Rhodococcus sp]]
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[[Category: Tesmer, J J.G.]]
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[[Category: Nance, M R]]
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[[Category: Tesmer, J J.G]]
[[Category: Alpha/beta hydrolase]]
[[Category: Alpha/beta hydrolase]]
[[Category: Esterase]]
[[Category: Esterase]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]

Revision as of 06:08, 18 December 2014

Thermostable Cocaine Esterase with mutations L169K and G173Q, bound to DTT adduct

3ida, resolution 1.60Å

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