Structural highlights
2jf0 is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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Ligands: | , |
NonStd Res: | |
Related: | 1c2b, 1c2o, 1j06, 1j07, 1ku6, 1maa, 1mah, 1n5m, 1n5r, 1q83, 1q84, 2c0p, 2c0q, 2h9y, 2ha0, 2ha2, 2ha3, 2ha4, 2ha5, 2ha6, 2ha7, 2jey, 2jez |
Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[ACES_MOUSE] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft.
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
Organophosphorus compound-based nerve agents inhibit the essential enzyme acetylcholinesterase (AChE) causing acute toxicity and death. Clinical treatment of nerve-agent poisoning is to use oxime-based antidotes to reactivate the inhibited AChE. However, the nerve agent tabun is resistant to oximes. To design improved oximes, crystal structures of a tabun-conjugated AChE in complex with different oximes are needed to guide the structural modifications of known antidotes. However, this type of structure is extremely challenging to obtain because both deamidation of the tabun conjugate and reactivation of AChE occur during crystallographic experiments. Here we report, for the first time, the crystal structures of Ortho-7 and HLo-7 in complex with AChE that is conjugated to an intact tabun. These structures were determined by our new strategy of combining crystallographic and mass spectrometric analyses of AChE crystals. The results explain the relative reactivation potencies of the two oximes and offer insights into improving known medical antidotes.
Novel nerve-agent antidote design based on crystallographic and mass spectrometric analyses of tabun-conjugated acetylcholinesterase in complex with antidotes.,Ekstrom FJ, Astot C, Pang YP Clin Pharmacol Ther. 2007 Sep;82(3):282-93. Epub 2007 Apr 18. PMID:17443135[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ekstrom FJ, Astot C, Pang YP. Novel nerve-agent antidote design based on crystallographic and mass spectrometric analyses of tabun-conjugated acetylcholinesterase in complex with antidotes. Clin Pharmacol Ther. 2007 Sep;82(3):282-93. Epub 2007 Apr 18. PMID:17443135