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1mx5

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Revision as of 08:02, 31 July 2019

Crystal Structure of Human Liver Carboxylesterase in complexed with homatropine, a cocaine analogue

Structural highlights

1mx5 is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	1mx1, 1mx9
Activity:	Carboxylesterase, with EC number 3.1.1.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[EST1_HUMAN] Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate.^[1] ^[2]

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

We present the first crystal structures of a human protein bound to analogs of cocaine and heroin. Human carboxylesterase 1 (hCE1) is a broad-spectrum bioscavenger that catalyzes the hydrolysis of heroin and cocaine, and the detoxification of organophosphate chemical weapons, such as sarin, soman and tabun. Crystal structures of the hCE1 glycoprotein in complex with the cocaine analog homatropine and the heroin analog naloxone provide explicit details about narcotic metabolism in humans. The hCE1 active site contains both specific and promiscuous compartments, which enable the enzyme to act on structurally distinct chemicals. A selective surface ligand-binding site regulates the trimer-hexamer equilibrium of hCE1 and allows each hCE1 monomer to bind two narcotic molecules simultaneously. The bioscavenger properties of hCE1 can likely be used to treat both narcotic overdose and chemical weapon exposure.

Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme.,Bencharit S, Morton CL, Xue Y, Potter PM, Redinbo MR Nat Struct Biol. 2003 May;10(5):349-56. PMID:12679808^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Brzezinski MR, Abraham TL, Stone CL, Dean RA, Bosron WF. Purification and characterization of a human liver cocaine carboxylesterase that catalyzes the production of benzoylecgonine and the formation of cocaethylene from alcohol and cocaine. Biochem Pharmacol. 1994 Nov 1;48(9):1747-55. PMID:7980644
↑ Pindel EV, Kedishvili NY, Abraham TL, Brzezinski MR, Zhang J, Dean RA, Bosron WF. Purification and cloning of a broad substrate specificity human liver carboxylesterase that catalyzes the hydrolysis of cocaine and heroin. J Biol Chem. 1997 Jun 6;272(23):14769-75. PMID:9169443
↑ Bencharit S, Morton CL, Xue Y, Potter PM, Redinbo MR. Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme. Nat Struct Biol. 2003 May;10(5):349-56. PMID:12679808 doi:10.1038/nsb919

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/1mx5"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Human Liver Carboxylesterase in complexed with homatropine, a cocaine analogue==
-<StructureSection load='1mx5' size='340' side='right' caption='[[1mx5]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+<StructureSection load='1mx5' size='340' side='right'caption='[[1mx5]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1mx5]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MX5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1MX5 FirstGlance]. <br>
@@ Line 15: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mx/1mx5_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mx/1mx5_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 30: / Line 30: @@
 </div>
 <div class="pdbe-citations 1mx5" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Carboxylesterase 3D structures|Carboxylesterase 3D structures]]
+*[[Cocaethylene Synthesis and Pathophysiology|Cocaethylene Synthesis and Pathophysiology]]
 == References ==
 <references/>
@@ Line 36: / Line 40: @@
 [[Category: Carboxylesterase]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Bencharit, S]]
 [[Category: Morton, C L]]

1mx5

From Proteopedia

Revision as of 08:02, 31 July 2019

Crystal Structure of Human Liver Carboxylesterase in complexed with homatropine, a cocaine analogue

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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