First time at Proteopedia? Click on the green links: they change the 3D image. Click and drag the molecules. Proteopedia is a 3D, interactive encyclopedia of proteins, RNA, DNA and other molecules. With a free user account, you can edit pages in Proteopedia. Visit the Main Page to learn more.

2hrr

From Proteopedia

Jump to: navigation, search
2hrr, resolution 2.70Å ()
Ligands: , , , ,
Gene: CES1 (Homo sapiens)
Activity: Carboxylesterase, with EC number 3.1.1.1
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

Crystal structure of Human Liver Carboxylesterase 1 (hCE1) in covalent complex with the nerve agent Tabun (GA)

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.

About this Structure

2hrr is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

Reference

  • Fleming CD, Edwards CC, Kirby SD, Maxwell DM, Potter PM, Cerasoli DM, Redinbo MR. Crystal structures of human carboxylesterase 1 in covalent complexes with the chemical warfare agents soman and tabun. Biochemistry. 2007 May 1;46(17):5063-71. Epub 2007 Apr 4. PMID:17407327 doi:10.1021/bi700246n

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools