2hrr

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)

Structural highlights 2hrr is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , , Gene: CES1 (Homo sapiens) Activity: Carboxylesterase, with EC number 3.1.1.1 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Carboxylesterase

spinqualitylabelsall models 2hrr, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image