|
|
| Line 1: |
Line 1: |
| [[Image:2hrr.jpg|left|200px]] | | {{Seed}} |
| | [[Image:2hrr.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_2hrr| PDB=2hrr | SCENE= }} | | {{STRUCTURE_2hrr| PDB=2hrr | SCENE= }} |
|
| |
|
| '''Crystal structure of Human Liver Carboxylesterase 1 (hCE1) in covalent complex with the nerve agent Tabun (GA)'''
| | ===Crystal structure of Human Liver Carboxylesterase 1 (hCE1) in covalent complex with the nerve agent Tabun (GA)=== |
|
| |
|
|
| |
|
| ==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. | | The line below this paragraph, {{ABSTRACT_PUBMED_17407327}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17407327 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_17407327}} |
|
| |
|
| ==About this Structure== | | ==About this Structure== |
| Line 28: |
Line 32: |
| [[Category: Hydrolase]] | | [[Category: Hydrolase]] |
| [[Category: Tabun]] | | [[Category: Tabun]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:38:09 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 19:02:16 2008'' |