1mx1: Difference between revisions

Revision as of 01:49, 3 May 2008

Crystal Structure of Human Liver Carboxylesterase in complex with tacrine

OverviewOverview

Human carboxylesterase 1 (hCE1) is a broad-spectrum bioscavenger that plays important roles in narcotic metabolism, clinical prodrug activation, and the processing of fatty acid and cholesterol derivatives. We determined the 2.4 A crystal structure of hCE1 in complex with tacrine, the first drug approved for treating Alzheimer's disease, and compare this structure to the Torpedo californica acetylcholinesterase (AcChE)-tacrine complex. Tacrine binds in multiple orientations within the catalytic gorge of hCE1, while it stacks in the smaller AcChE active site between aromatic side chains. Our results show that hCE1's promiscuous action on distinct substrates is enhanced by its ability to interact with ligands in multiple orientations at once. Further, we use our structure to identify tacrine derivatives that act as low-micromolar inhibitors of hCE1 and may provide new avenues for treating narcotic abuse and cholesterol-related diseases.

About this StructureAbout this Structure

1MX1 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of human carboxylesterase 1 complexed with the Alzheimer's drug tacrine: from binding promiscuity to selective inhibition., Bencharit S, Morton CL, Hyatt JL, Kuhn P, Danks MK, Potter PM, Redinbo MR, Chem Biol. 2003 Apr;10(4):341-9. PMID:12725862 Page seeded by OCA on Sat May 3 01:49:26 2008

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OCA

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 [[Image:1mx1.gif|left|200px]]
- {{Structure
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-|ACTIVITY= <span class='plainlinks'>[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] </span>
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-}}
 '''Crystal Structure of Human Liver Carboxylesterase in complex with tacrine'''
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 [[Category: Potter, P M.]]
 [[Category: Redinbo, M R.]]
-[[Category: esterase]]
+[[Category: Esterase]]
-[[Category: esterase inhibitor]]
+[[Category: Esterase inhibitor]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 01:49:26 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:22:20 2008''