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2hrr
From Proteopedia
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| - | [[Image:2hrr.jpg|left|200px]] | + | [[Image:2hrr.jpg|left|200px]] |
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| - | '''Crystal structure of Human Liver Carboxylesterase 1 (hCE1) in covalent complex with the nerve agent Tabun (GA)''' | + | {{Structure |
| + | |PDB= 2hrr |SIZE=350|CAPTION= <scene name='initialview01'>2hrr</scene>, resolution 2.70Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene>, <scene name='pdbligand=SUC:SUCROSE'>SUC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=NTJ:R-ETHYL N,N-DIMETHYLPHOSPHONAMIDATE'>NTJ</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= CES1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of Human Liver Carboxylesterase 1 (hCE1) in covalent complex with the nerve agent Tabun (GA)''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2HRR is a [ | + | 2HRR 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=2HRR OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structures of human carboxylesterase 1 in covalent complexes with the chemical warfare agents soman and tabun., Fleming CD, Edwards CC, Kirby SD, Maxwell DM, Potter PM, Cerasoli DM, Redinbo MR, Biochemistry. 2007 May 1;46(17):5063-71. Epub 2007 Apr 4. PMID:[http:// | + | Crystal structures of human carboxylesterase 1 in covalent complexes with the chemical warfare agents soman and tabun., Fleming CD, Edwards CC, Kirby SD, Maxwell DM, Potter PM, Cerasoli DM, Redinbo MR, Biochemistry. 2007 May 1;46(17):5063-71. Epub 2007 Apr 4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17407327 17407327] |
[[Category: Carboxylesterase]] | [[Category: Carboxylesterase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: tabun]] | [[Category: tabun]] | ||
| - | ''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 17:20:52 2008'' |
Revision as of 15:20, 20 March 2008
| |||||||
| , resolution 2.70Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , and | ||||||
| Gene: | CES1 (Homo sapiens) | ||||||
| Activity: | Carboxylesterase, with EC number 3.1.1.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of Human Liver Carboxylesterase 1 (hCE1) in covalent complex with the nerve agent Tabun (GA)
Contents |
Overview
The organophosphorus nerve agents sarin, soman, tabun, and VX exert their toxic effects by inhibiting the action of human acetylcholinesterase, a member of the serine hydrolase superfamily of enzymes. The current treatments for nerve agent exposure must be administered quickly to be effective, and they often do not eliminate long-term toxic side effects associated with organophosphate poisoning. Thus, there is significant need for effective prophylactic methods to protect at-risk personnel from nerve agent exposure, and protein-based approaches have emerged as promising candidates. We present the 2.7 A resolution crystal structures of the serine hydrolase human carboxylesterase 1 (hCE1), a broad-spectrum drug metabolism enzyme, in covalent acyl-enzyme intermediate complexes with the chemical weapons soman and tabun. The structures reveal that hCE1 binds stereoselectively to these nerve agents; for example, hCE1 appears to react preferentially with the 10(4)-fold more lethal PS stereoisomer of soman relative to the PR form. In addition, structural features of the hCE1 active site indicate that the enzyme may be resistant to dead-end organophosphate aging reactions that permanently inactivate other serine hydrolases. Taken together, these data provide important structural details toward the goal of engineering hCE1 into an organophosphate hydrolase and protein-based therapeutic for nerve agent exposure.
Disease
Known disease associated with this structure: Monocyte carboxylesterase deficiency (1) OMIM:[114835]
About this Structure
2HRR is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structures of human carboxylesterase 1 in covalent complexes with the chemical warfare agents soman and tabun., Fleming CD, Edwards CC, Kirby SD, Maxwell DM, Potter PM, Cerasoli DM, Redinbo MR, Biochemistry. 2007 May 1;46(17):5063-71. Epub 2007 Apr 4. PMID:17407327
Page seeded by OCA on Thu Mar 20 17:20:52 2008
Categories: Carboxylesterase | Homo sapiens | Single protein | Fleming, C D. | Redinbo, M R. | NAG | NTJ | SIA | SO4 | SUC | Hydrolase | Tabun
