2jez: Difference between revisions

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.Clinical, Pharmacology & Therapeutics advance online publication, 18 April 2007;, doi:10.1038/sj.clpt.6100151.

2JEZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with HLO and P6G as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2JEZ OCA].  

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