3i2f

From Proteopedia

(Difference between revisions)

Revision as of 15:37, 4 August 2016

Cocaine Esterase with mutations T172R / G173Q, bound to DTT adduct

Structural highlights

3i2f is a 1 chain structure with sequence from Rhosm. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	1ju3, 1ju4, 1l7r, 1l7q, 3i2g, 3i2h, 3i2i, 3i2j, 3i2k
Gene:	Cocaine Esterase, cocE (RHOSM)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 PubMed

Cocaine 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.

References

↑ Bresler MM, Rosser SJ, Basran A, Bruce NC. Gene cloning and nucleotide sequencing and properties of a cocaine esterase from Rhodococcus sp. strain MB1. Appl Environ Microbiol. 2000 Mar;66(3):904-8. PMID:10698749
↑ Cooper ZD, Narasimhan D, Sunahara RK, Mierzejewski P, Jutkiewicz EM, Larsen NA, Wilson IA, Landry DW, Woods JH. Rapid and robust protection against cocaine-induced lethality in rats by the bacterial cocaine esterase. Mol Pharmacol. 2006 Dec;70(6):1885-91. Epub 2006 Sep 12. PMID:16968810 doi:10.1124/mol.106.025999
↑ Turner JM, Larsen NA, Basran A, Barbas CF 3rd, Bruce NC, Wilson IA, Lerner RA. Biochemical characterization and structural analysis of a highly proficient cocaine esterase. Biochemistry. 2002 Oct 15;41(41):12297-307. PMID:12369817
↑ Narasimhan D, Nance MR, Gao D, Ko MC, Macdonald J, Tamburi P, Yoon D, Landry DM, Woods JH, Zhan CG, Tesmer JJ, Sunahara RK. Structural analysis of thermostabilizing mutations of cocaine esterase. Protein Eng Des Sel. 2010 Jul;23(7):537-47. Epub 2010 Apr 30. PMID:20436035 doi:10.1093/protein/gzq025

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/3i2f"

Categories: Rhosm | Nance, M R | Tesmer, J J.G | Alpha/beta hydrolase | Hydrolase

@@ Line 1: / Line 1: @@
 ==Cocaine Esterase with mutations T172R / G173Q, bound to DTT adduct==
 <StructureSection load='3i2f' size='340' side='right' caption='[[3i2f]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3i2f]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Rhodococcus_sp._mb1_'bresler_1999' Rhodococcus sp. mb1 'bresler 1999']. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I2F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3I2F FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3i2f]] 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=3I2F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3I2F 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>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ju3|1ju3]], [[1ju4|1ju4]], [[1l7r|1l7r]], [[1l7q|1l7q]], [[3i2g|3i2g]], [[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 Rhodococcus sp. MB1 'Bresler 1999'])</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 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=3i2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i2f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3i2f RCSB], [http://www.ebi.ac.uk/pdbsum/3i2f 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=3i2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i2f OCA], [http://pdbe.org/3i2f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3i2f RCSB], [http://www.ebi.ac.uk/pdbsum/3i2f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3i2f ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
     <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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=3i2f ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 28: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3i2f" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 35: / Line 37: @@
 __TOC__
 </StructureSection>
-[[Category: Rhodococcus sp. mb1 'bresler 1999']]
+[[Category: Rhosm]]
 [[Category: Nance, M R]]
 [[Category: Tesmer, J J.G]]
 [[Category: Alpha/beta hydrolase]]
 [[Category: Hydrolase]]

3i2f

From Proteopedia

Revision as of 15:37, 4 August 2016

Cocaine Esterase with mutations T172R / G173Q, bound to DTT adduct

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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