9k48

From Proteopedia

(Difference between revisions)

Current revision

Bacetrial Cocaine Esterase with mutations T172R/G173Q/V116K/S117A/A51K

Structural highlights

9k48 is a 1 chain structure with sequence from Rhodococcus sp. MB1 'Bresler 1999'. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.249Å
Ligands:
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]

Publication Abstract from PubMed

Enzyme therapy for cocaine detoxification should break down both cocaine and its primary toxic metabolite, benzoylecgonine (BZE), which is also the main form of cocaine contaminant in the environment. An ideal BZE-metabolizing enzyme (BZEase) is expected to be highly efficient and selective in BZE hydrolysis. Here, BZEase4 was engineered from bacterial cocaine esterase (CocE) by our reactant state-based enzyme design theories (RED), which has a 34,977-fold improved substrate discrimination between BZE and the neurotransmitter acetylcholine (ACh), compared with wild-type CocE. Under the physiological concentrations of BZE and ACh, the reaction velocity of BZEase4 against BZE is 2.25 x 10(6)-fold higher than it against ACh, suggesting BZEase4 has extremely high substrate selectivity for BZE over ACh to minimize the potential cholinergic side-effects. This study provides additional evidence supporting the further development of BZEase4 toward a promising therapeutic for cocaine overdose, a potentially effective and eco-friendly enzymatic method for BZE degradation in the environment.

Catalytic mechanism, computational design, and crystal structure of a highly specific and efficient benzoylecgonine hydrolase.,Chen X, Zhang Y, Tong J, Ouyang P, Deng X, Zhang J, Liu H, Hu Y, Yao W, Wang J, Wang X, Hou S, Yao J Int J Biol Macromol. 2024 Dec;283(Pt 3):137767. doi: , 10.1016/j.ijbiomac.2024.137767. Epub 2024 Nov 17. PMID:39561846^[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
↑ Chen X, Zhang Y, Tong J, Ouyang P, Deng X, Zhang J, Liu H, Hu Y, Yao W, Wang J, Wang X, Hou S, Yao J. Catalytic mechanism, computational design, and crystal structure of a highly specific and efficient benzoylecgonine hydrolase. Int J Biol Macromol. 2024 Dec;283(Pt 3):137767. PMID:39561846 doi:10.1016/j.ijbiomac.2024.137767

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9k48"

Categories: Large Structures | Rhodococcus sp. MB1 'Bresler 1999' | Tong JS | Zhang Y

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9k48 is ON HOLD  until Paper Publication
+==Bacetrial Cocaine Esterase with mutations T172R/G173Q/V116K/S117A/A51K==
+<StructureSection load='9k48' size='340' side='right'caption='[[9k48]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9k48]] is a 1 chain structure with sequence from [https://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=9K48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9K48 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.249&#8491;</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></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=9k48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9k48 OCA], [https://pdbe.org/9k48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9k48 RCSB], [https://www.ebi.ac.uk/pdbsum/9k48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9k48 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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Enzyme therapy for cocaine detoxification should break down both cocaine and its primary toxic metabolite, benzoylecgonine (BZE), which is also the main form of cocaine contaminant in the environment. An ideal BZE-metabolizing enzyme (BZEase) is expected to be highly efficient and selective in BZE hydrolysis. Here, BZEase4 was engineered from bacterial cocaine esterase (CocE) by our reactant state-based enzyme design theories (RED), which has a 34,977-fold improved substrate discrimination between BZE and the neurotransmitter acetylcholine (ACh), compared with wild-type CocE. Under the physiological concentrations of BZE and ACh, the reaction velocity of BZEase4 against BZE is 2.25 x 10(6)-fold higher than it against ACh, suggesting BZEase4 has extremely high substrate selectivity for BZE over ACh to minimize the potential cholinergic side-effects. This study provides additional evidence supporting the further development of BZEase4 toward a promising therapeutic for cocaine overdose, a potentially effective and eco-friendly enzymatic method for BZE degradation in the environment.
-Authors: Zhang, Y., Tong, J.S.
+Catalytic mechanism, computational design, and crystal structure of a highly specific and efficient benzoylecgonine hydrolase.,Chen X, Zhang Y, Tong J, Ouyang P, Deng X, Zhang J, Liu H, Hu Y, Yao W, Wang J, Wang X, Hou S, Yao J Int J Biol Macromol. 2024 Dec;283(Pt 3):137767. doi: , 10.1016/j.ijbiomac.2024.137767. Epub 2024 Nov 17. PMID:39561846<ref>PMID:39561846</ref>
-Description: Bacetrial Cocaine Esterase with mutations T172R/G173Q/V116K/S117A/A51K
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Tong, J.S]]
+<div class="pdbe-citations 9k48" style="background-color:#fffaf0;"></div>
-[[Category: Zhang, Y]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Rhodococcus sp. MB1 'Bresler 1999']]
+[[Category: Tong JS]]
+[[Category: Zhang Y]]

9k48

From Proteopedia

Current revision

Bacetrial Cocaine Esterase with mutations T172R/G173Q/V116K/S117A/A51K

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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