2jf0
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Organophosphorus compound-based nerve agents inhibit the essential enzyme | + | 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. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | Novel | + | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17443135 17443135] |
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Astot, C.]] | [[Category: Astot, C.]] | ||
[[Category: Ekstrom, F.]] | [[Category: Ekstrom, F.]] | ||
| - | [[Category: Pang, Y | + | [[Category: Pang, Y P.]] |
[[Category: HBP]] | [[Category: HBP]] | ||
[[Category: P6G]] | [[Category: P6G]] | ||
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[[Category: tabun]] | [[Category: tabun]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:02:33 2008'' |
Revision as of 16:02, 21 February 2008
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MUS MUSCULUS ACETYLCHOLINESTERASE IN COMPLEX WITH TABUN AND ORTHO-7
Overview
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.
About this Structure
2JF0 is a Single protein structure of sequence from Mus musculus with and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 18:02:33 2008
Categories: Mus musculus | Single protein | Astot, C. | Ekstrom, F. | Pang, Y P. | HBP | P6G | Acetylcholinesterase | Alternative splicing | Glycoprotein | Hydrolase | Membrane | Mouse | Neurotransmitter degradation | Ortho-7 | Oxime | Serine esterase | Synapse | Tabun
