3ida: Difference between revisions

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{{Seed}}
[[Image:3ida.jpg|left|200px]]


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==Thermostable Cocaine Esterase with mutations L169K and G173Q, bound to DTT adduct==
The line below this paragraph, containing "STRUCTURE_3ida", creates the "Structure Box" on the page.
<StructureSection load='3ida' size='340' side='right'caption='[[3ida]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[3ida]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rhodococcus_sp._MB1 Rhodococcus sp. MB1]. 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 [https://proteopedia.org/fgij/fg.htm?mol=3IDA FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>
{{STRUCTURE_3ida|  PDB=3ida  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ida FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ida OCA], [https://pdbe.org/3ida PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ida RCSB], [https://www.ebi.ac.uk/pdbsum/3ida PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ida ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/COCE_RHOSM 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.<ref>PMID:10698749</ref> <ref>PMID:16968810</ref> <ref>PMID:12369817</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/id/3ida_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </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/main_output.php?pdb_ID=3ida ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


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


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3ida" style="background-color:#fffaf0;"></div>


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==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_20086035}}, adds the Publication Abstract to the page
*[[Cocaine esterase|Cocaine esterase]]
(as it appears on PubMed at http://www.pubmed.gov), where 20086035 is the PubMed ID number.
== References ==
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<references/>
{{ABSTRACT_PUBMED_20086035}}
__TOC__
 
</StructureSection>
==About this Structure==
[[Category: Large Structures]]
3IDA is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Rhodococcus_sp._mb1 Rhodococcus sp. mb1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IDA OCA].
[[Category: Rhodococcus sp. MB1]]
 
[[Category: Nance MR]]
==Reference==
[[Category: Tesmer JJG]]
<ref group="xtra">PMID:20086035</ref><references group="xtra"/>
[[Category: Rhodococcus sp. mb1]]
[[Category: Nance, M R.]]
[[Category: Tesmer, J J.G.]]
[[Category: Alpha/beta hydrolase]]
[[Category: Cytoplasm]]
[[Category: Esterase]]
[[Category: Hydrolase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar  3 16:00:30 2010''
Retrieved from "https://proteopedia.org/3ida"