1mx5
From Proteopedia
(New page: 200px<br /> <applet load="1mx5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mx5, resolution 2.80Å" /> '''Crystal Structure o...) |
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| - | [[Image:1mx5.gif|left|200px]]<br /> | + | [[Image:1mx5.gif|left|200px]]<br /><applet load="1mx5" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1mx5" size=" | + | |
caption="1mx5, resolution 2.80Å" /> | caption="1mx5, resolution 2.80Å" /> | ||
'''Crystal Structure of Human Liver Carboxylesterase in complexed with homatropine, a cocaine analogue'''<br /> | '''Crystal Structure of Human Liver Carboxylesterase in complexed with homatropine, a cocaine analogue'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We present the first crystal structures of a human protein bound to | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1MX5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG, NDG, SIA, CL and HTQ as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Carboxylesterase Carboxylesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.1 3.1.1.1] Full crystallographic information is available from [http:// | + | 1MX5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=NDG:'>NDG</scene>, <scene name='pdbligand=SIA:'>SIA</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=HTQ:'>HTQ</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Carboxylesterase Carboxylesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.1 3.1.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MX5 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bencharit, S.]] | [[Category: Bencharit, S.]] | ||
| - | [[Category: Morton, C | + | [[Category: Morton, C L.]] |
| - | [[Category: Potter, P | + | [[Category: Potter, P M.]] |
| - | [[Category: Redinbo, M | + | [[Category: Redinbo, M R.]] |
[[Category: Xue, Y.]] | [[Category: Xue, Y.]] | ||
[[Category: CL]] | [[Category: CL]] | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:59:58 2008'' |
Revision as of 11:59, 21 February 2008
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Crystal Structure of Human Liver Carboxylesterase in complexed with homatropine, a cocaine analogue
Contents |
Overview
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.
Disease
Known disease associated with this structure: Monocyte carboxylesterase deficiency (1) OMIM:[114835]
About this Structure
1MX5 is a Single protein structure of sequence from Homo sapiens with , , , and as ligands. Active as Carboxylesterase, with EC number 3.1.1.1 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 13:59:58 2008
Categories: Carboxylesterase | Homo sapiens | Single protein | Bencharit, S. | Morton, C L. | Potter, P M. | Redinbo, M R. | Xue, Y. | CL | HTQ | NAG | NDG | SIA | Cocaine | Esterase | Hydrolase
