1ya4
From Proteopedia
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| - | [[Image:1ya4.gif|left|200px]] | + | [[Image:1ya4.gif|left|200px]] |
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| - | '''Crystal Structure of Human Liver Carboxylesterase 1 in complex with tamoxifen''' | + | {{Structure |
| + | |PDB= 1ya4 |SIZE=350|CAPTION= <scene name='initialview01'>1ya4</scene>, resolution 3.20Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=CTX:(Z)-2-[4-(1,2)-DIPHENYL-1-BUTENYL)-PHENOXY]-N,N-DIMETHYLETHANAMINE'>CTX</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''Crystal Structure of Human Liver Carboxylesterase 1 in complex with tamoxifen''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1YA4 is a [ | + | 1YA4 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YA4 OCA]. |
==Reference== | ==Reference== | ||
| - | Structural insights into drug processing by human carboxylesterase 1: tamoxifen, mevastatin, and inhibition by benzil., Fleming CD, Bencharit S, Edwards CC, Hyatt JL, Tsurkan L, Bai F, Fraga C, Morton CL, Howard-Williams EL, Potter PM, Redinbo MR, J Mol Biol. 2005 Sep 9;352(1):165-77. PMID:[http:// | + | Structural insights into drug processing by human carboxylesterase 1: tamoxifen, mevastatin, and inhibition by benzil., Fleming CD, Bencharit S, Edwards CC, Hyatt JL, Tsurkan L, Bai F, Fraga C, Morton CL, Howard-Williams EL, Potter PM, Redinbo MR, J Mol Biol. 2005 Sep 9;352(1):165-77. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16081098 16081098] |
[[Category: Carboxylesterase]] | [[Category: Carboxylesterase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: tamoxifen complex]] | [[Category: tamoxifen complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:20:13 2008'' |
Revision as of 13:20, 20 March 2008
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| , resolution 3.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Activity: | Carboxylesterase, with EC number 3.1.1.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of Human Liver Carboxylesterase 1 in complex with tamoxifen
Contents |
Overview
Human carboxylesterase 1 (hCE1) exhibits broad substrate specificity and is involved in xenobiotic processing and endobiotic metabolism. We present and analyze crystal structures of hCE1 in complexes with the cholesterol-lowering drug mevastatin, the breast cancer drug tamoxifen, the fatty acyl ethyl ester (FAEE) analogue ethyl acetate, and the novel hCE1 inhibitor benzil. We find that mevastatin does not appear to be a substrate for hCE1, and instead acts as a partially non-competitive inhibitor of the enzyme. Similarly, we show that tamoxifen is a low micromolar, partially non-competitive inhibitor of hCE1. Further, we describe the structural basis for the inhibition of hCE1 by the nanomolar-affinity dione benzil, which acts by forming both covalent and non-covalent complexes with the enzyme. Our results provide detailed insights into the catalytic and non-catalytic processing of small molecules by hCE1, and suggest that the efficacy of clinical drugs may be modulated by targeted hCE1 inhibitors.
Disease
Known disease associated with this structure: Monocyte carboxylesterase deficiency (1) OMIM:[114835]
About this Structure
1YA4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural insights into drug processing by human carboxylesterase 1: tamoxifen, mevastatin, and inhibition by benzil., Fleming CD, Bencharit S, Edwards CC, Hyatt JL, Tsurkan L, Bai F, Fraga C, Morton CL, Howard-Williams EL, Potter PM, Redinbo MR, J Mol Biol. 2005 Sep 9;352(1):165-77. PMID:16081098
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