7f65: Difference between revisions
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==Bacetrial Cocaine Esterase with mutations T172R/G173Q/V116K/S117A/A51L, bound to benzoic acid== | ==Bacetrial Cocaine Esterase with mutations T172R/G173Q/V116K/S117A/A51L, bound to benzoic acid== | ||
<StructureSection load='7f65' size='340' side='right'caption='[[7f65]]' scene=''> | <StructureSection load='7f65' size='340' side='right'caption='[[7f65]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7F65 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F65 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7f65]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7F65 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F65 FirstGlance]. <br> | ||
</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=7f65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f65 OCA], [https://pdbe.org/7f65 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f65 RCSB], [https://www.ebi.ac.uk/pdbsum/7f65 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f65 ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Cocaine_esterase Cocaine esterase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.84 3.1.1.84] </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=7f65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f65 OCA], [https://pdbe.org/7f65 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f65 RCSB], [https://www.ebi.ac.uk/pdbsum/7f65 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f65 ProSAT]</span></td></tr> | |||
</table> | </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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Benzoylecgonine (BZE) is the major toxic metabolite of cocaine and is responsible for the long-term cocaine-induced toxicity owing to its long residence time in humans. BZE is also the main contaminant following cocaine consumption. Here, we identified the bacterial cocaine esterase (CocE) as a BZE-metabolizing enzyme (BZEase), which can degrade BZE into biological inactive metabolites (ecgonine and benzoic acid). CocE was redesigned by a reactant-state-based enzyme design theory. An encouraging mutant denoted as BZEase2, presented a >400-fold improved catalytic efficiency against BZE compared with wild-type (WT) CocE. In vivo, a single dose of BZEase2 (1 mg kg(-1) , IV) could eliminate nearly all BZE within only two minutes, suggesting the enzyme has the potential for cocaine overdose treatment and BZE elimination in the environment by accelerating BZE clearance. The crystal structure of a designed BZEase was also determined. | |||
Computational Design and Crystal Structure of a Highly Efficient Benzoylecgonine Hydrolase.,Chen X, Deng X, Zhang Y, Wu Y, Yang K, Li Q, Wang J, Yao W, Tong J, Xie T, Hou S, Yao J Angew Chem Int Ed Engl. 2021 Aug 5. doi: 10.1002/anie.202108559. PMID:34351032<ref>PMID:34351032</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7f65" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Cocaine esterase]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Ouyang | [[Category: Ouyang, P F]] | ||
[[Category: Tong J]] | [[Category: Tong, J]] | ||
[[Category: Zhang Y]] | [[Category: Zhang, Y]] | ||
[[Category: Benzoylecgonine metabolism]] | |||
[[Category: Hydrolase]] | |||
[[Category: Mutantion]] | |||
Revision as of 13:58, 16 February 2022
Bacetrial Cocaine Esterase with mutations T172R/G173Q/V116K/S117A/A51L, bound to benzoic acidBacetrial Cocaine Esterase with mutations T172R/G173Q/V116K/S117A/A51L, bound to benzoic acid
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] Publication Abstract from PubMedBenzoylecgonine (BZE) is the major toxic metabolite of cocaine and is responsible for the long-term cocaine-induced toxicity owing to its long residence time in humans. BZE is also the main contaminant following cocaine consumption. Here, we identified the bacterial cocaine esterase (CocE) as a BZE-metabolizing enzyme (BZEase), which can degrade BZE into biological inactive metabolites (ecgonine and benzoic acid). CocE was redesigned by a reactant-state-based enzyme design theory. An encouraging mutant denoted as BZEase2, presented a >400-fold improved catalytic efficiency against BZE compared with wild-type (WT) CocE. In vivo, a single dose of BZEase2 (1 mg kg(-1) , IV) could eliminate nearly all BZE within only two minutes, suggesting the enzyme has the potential for cocaine overdose treatment and BZE elimination in the environment by accelerating BZE clearance. The crystal structure of a designed BZEase was also determined. Computational Design and Crystal Structure of a Highly Efficient Benzoylecgonine Hydrolase.,Chen X, Deng X, Zhang Y, Wu Y, Yang K, Li Q, Wang J, Yao W, Tong J, Xie T, Hou S, Yao J Angew Chem Int Ed Engl. 2021 Aug 5. doi: 10.1002/anie.202108559. PMID:34351032[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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