1mx1
From Proteopedia
(New page: 200px<br /> <applet load="1mx1" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mx1, resolution 2.40Å" /> '''Crystal Structure o...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1mx1.gif|left|200px]]<br /> | + | [[Image:1mx1.gif|left|200px]]<br /><applet load="1mx1" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1mx1" size=" | + | |
caption="1mx1, resolution 2.40Å" /> | caption="1mx1, resolution 2.40Å" /> | ||
'''Crystal Structure of Human Liver Carboxylesterase in complex with tacrine'''<br /> | '''Crystal Structure of Human Liver Carboxylesterase in complex with tacrine'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human carboxylesterase 1 (hCE1) is a broad-spectrum bioscavenger that | + | 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. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1MX1 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, SIA and THA 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:// | + | 1MX1 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=SIA:'>SIA</scene> and <scene name='pdbligand=THA:'>THA</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=1MX1 OCA]. |
==Reference== | ==Reference== | ||
| Line 19: | Line 18: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bencharit, S.]] | [[Category: Bencharit, S.]] | ||
| - | [[Category: Danks, M | + | [[Category: Danks, M K.]] |
| - | [[Category: Hyatt, J | + | [[Category: Hyatt, J L.]] |
[[Category: Kuhn, P.]] | [[Category: Kuhn, P.]] | ||
| - | [[Category: Morton, C | + | [[Category: Morton, C L.]] |
| - | [[Category: Potter, P | + | [[Category: Potter, P M.]] |
| - | [[Category: Redinbo, M | + | [[Category: Redinbo, M R.]] |
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: SIA]] | [[Category: SIA]] | ||
| Line 32: | Line 31: | ||
[[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
|
Crystal Structure of Human Liver Carboxylesterase in complex with tacrine
Contents |
Overview
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.
Disease
Known disease associated with this structure: Monocyte carboxylesterase deficiency (1) OMIM:[114835]
About this Structure
1MX1 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
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 Thu Feb 21 13:59:58 2008
Categories: Carboxylesterase | Homo sapiens | Single protein | Bencharit, S. | Danks, M K. | Hyatt, J L. | Kuhn, P. | Morton, C L. | Potter, P M. | Redinbo, M R. | NAG | SIA | THA | Esterase | Esterase inhibitor | Hydrolase
