1ju4: Difference between revisions

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New page: left|200px<br /><applet load="1ju4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ju4, resolution 1.63Å" /> '''BACTERIAL COCAINE ES...
 
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[[Image:1ju4.jpg|left|200px]]<br /><applet load="1ju4" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1ju4, resolution 1.63&Aring;" />
'''BACTERIAL COCAINE ESTERASE COMPLEX WITH PRODUCT'''<br />


==Overview==
==BACTERIAL COCAINE ESTERASE COMPLEX WITH PRODUCT==
Here we report the first structure of a cocaine-degrading enzyme. The, bacterial esterase, cocE, hydrolyzes pharmacologically active (-)-cocaine, to a non-psychoactive metabolite with a rate faster than any other, reported cocaine esterase (kcat = 7.8 s-1 and KM = 640 nM). Because of the, high catalytic proficiency of cocE, it is an attractive candidate for, novel protein-based therapies for cocaine overdose. The crystal structure, of cocE, solved by multiple anomalous dispersion (MAD) methods, reveals, that cocE is a serine esterase composed of three domains: (i) a canonical, alpha/beta hydrolase fold (ii) an alpha-helical domain that caps the, active site and (iii) a jelly-roll-like beta-domain that interacts, extensively with the other two domains. The active site was identified, within the interface of all three domains by analysis of the crystal, structures of transition state analog adduct and product complexes, which, were refined at 1.58 A and 1.63 A resolution, respectively. These, structural studies suggest that substrate recognition arises partly from, interactions between the benzoyl moiety of cocaine and a highly evolved, specificity pocket.
<StructureSection load='1ju4' size='340' side='right'caption='[[1ju4]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ju4]] 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=1JU4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JU4 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]] 1.63&#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=1ju4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ju4 OCA], [https://pdbe.org/1ju4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ju4 RCSB], [https://www.ebi.ac.uk/pdbsum/1ju4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ju4 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/ju/1ju4_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1ju4 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1JU4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rhodococcus_sp._mb1 Rhodococcus sp. mb1] with BEZ as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1JU4 OCA].
*[[Cocaine esterase|Cocaine esterase]]
 
== References ==
==Reference==
<references/>
Crystal structure of a bacterial cocaine esterase., Larsen NA, Turner JM, Stevens J, Rosser SJ, Basran A, Lerner RA, Bruce NC, Wilson IA, Nat Struct Biol. 2002 Jan;9(1):17-21. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11742345 11742345]
__TOC__
[[Category: Rhodococcus sp. mb1]]
</StructureSection>
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Basran, A.]]
[[Category: Rhodococcus sp. MB1]]
[[Category: Bruce, N.C.]]
[[Category: Basran A]]
[[Category: Larsen, N.A.]]
[[Category: Bruce NC]]
[[Category: Lerner, R.A.]]
[[Category: Larsen NA]]
[[Category: Rosser, S.J.]]
[[Category: Lerner RA]]
[[Category: Stevens, J.]]
[[Category: Rosser SJ]]
[[Category: Turner, J.M.]]
[[Category: Stevens J]]
[[Category: Wilson, I.A.]]
[[Category: Turner JM]]
[[Category: BEZ]]
[[Category: Wilson IA]]
[[Category: alpha/beta hydrolase]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 18:34:47 2007''

Latest revision as of 10:42, 7 February 2024

BACTERIAL COCAINE ESTERASE COMPLEX WITH PRODUCTBACTERIAL COCAINE ESTERASE COMPLEX WITH PRODUCT

Structural highlights

1ju4 is a 1 chain structure with sequence from Rhodococcus sp. MB1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.63Å
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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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

1ju4, resolution 1.63Å

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