1mx1: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1mx1.gif|left|200px]] | [[Image:1mx1.gif|left|200px]] | ||
'''Crystal Structure of Human Liver Carboxylesterase in complex with tacrine''' | {{Structure | ||
|PDB= 1mx1 |SIZE=350|CAPTION= <scene name='initialview01'>1mx1</scene>, resolution 2.40Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene> and <scene name='pdbligand=THA:TACRINE'>THA</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 in complex with tacrine''' | |||
==Overview== | ==Overview== | ||
| Line 10: | Line 19: | ||
==About this Structure== | ==About this Structure== | ||
1MX1 is a [ | 1MX1 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=1MX1 OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/12725862 12725862] | ||
[[Category: Carboxylesterase]] | [[Category: Carboxylesterase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| Line 31: | Line 40: | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
''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 12:49:19 2008'' | ||
Revision as of 13:49, 20 March 2008
| |||||||
| , resolution 2.40Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Activity: | Carboxylesterase, with EC number 3.1.1.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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.
DiseaseDisease
Known disease associated with this structure: Monocyte carboxylesterase deficiency (1) OMIM:[114835]
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 Thu Mar 20 12:49:19 2008