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3dl7

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Revision as of 05:40, 8 March 2018

Aged Form of Mouse Acetylcholinesterase Inhibited by Tabun- Update

Structural highlights

3dl7 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.
Ligands:	, , ,
NonStd Res:	,
Related:	2c0p, 2c0q, 3dkk, 3djy, 3dl4
Gene:	Ache (LK3 transgenic mice)
Activity:	Acetylcholinesterase, with EC number 3.1.1.7
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

Human butyrylcholinesterase (hBChE) hydrolyzes or scavenges a wide range of toxic esters, including heroin, cocaine, carbamate pesticides, organophosphorus pesticides, and nerve agents. Organophosphates (OPs) exert their acute toxicity through inhibition of acetylcholinesterase (AChE) by phosphylation of the catalytic serine. Phosphylated cholinesterase (ChE) can undergo a spontaneous, time-dependent process called "aging", during which the OP-ChE conjugate is dealkylated. This leads to irreversible inhibition of the enzyme. The inhibition of ChEs by tabun and the subsequent aging reaction are of particular interest, because tabun-ChE conjugates display an extraordinary resistance toward most current oxime reactivators. We investigated the structural basis of oxime resistance for phosphoramidated ChE conjugates by determining the crystal structures of the non-aged and aged forms of hBChE inhibited by tabun, and by updating the refinement of non-aged and aged tabun-inhibited mouse AChE (mAChE). Structures for non-aged and aged tabun-hBChE were refined to 2.3 and 2.1 A, respectively. The refined structures of aged ChE conjugates clearly show that the aging reaction proceeds through O-dealkylation of the P( R) enantiomer of tabun. After dealkylation, the negatively charged oxygen forms a strong salt bridge with protonated His438N2 that prevents reactivation. Mass spectrometric analysis of the aged tabun-inhibited hBChE showed that both the dimethylamine and ethoxy side chains were missing from the phosphorus. Loss of the ethoxy is consistent with the crystallography results. Loss of the dimethylamine is consistent with acid-catalyzed deamidation during the preparation of the aged adduct for mass spectrometry. The reported 3D data will help in the design of new oximes capable of reactivating tabun-ChE conjugates.

Aging of Cholinesterases Phosphylated by Tabun Proceeds through O-Dealkylation.,Carletti E, Li H, Li B, Ekstrom F, Nicolet Y, Loiodice M, Gillon E, Froment MT, Lockridge O, Schopfer LM, Masson P, Nachon F J Am Chem Soc. 2008 Nov 1. PMID:18975951^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Carletti E, Li H, Li B, Ekstrom F, Nicolet Y, Loiodice M, Gillon E, Froment MT, Lockridge O, Schopfer LM, Masson P, Nachon F. Aging of Cholinesterases Phosphylated by Tabun Proceeds through O-Dealkylation. J Am Chem Soc. 2008 Nov 1. PMID:18975951 doi:10.1021/ja804941z

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3dl7"

@@ Line 1: / Line 1: @@
 ==Aged Form of Mouse Acetylcholinesterase Inhibited by Tabun- Update==
 <StructureSection load='3dl7' size='340' side='right' caption='[[3dl7]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
@@ Line 8: / Line 9: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ache ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.7 3.1.1.7] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dl7 OCA], [http://pdbe.org/3dl7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dl7 RCSB], [http://www.ebi.ac.uk/pdbsum/3dl7 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dl7 OCA], [http://pdbe.org/3dl7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dl7 RCSB], [http://www.ebi.ac.uk/pdbsum/3dl7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3dl7 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dl/3dl7_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dl/3dl7_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 33: / Line 34: @@
 ==See Also==
-*[[3D structures of acetylcholinesterase|3D structures of acetylcholinesterase]]
+*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]]
 == References ==
 <references/>

3dl7

From Proteopedia

Revision as of 05:40, 8 March 2018

Aged Form of Mouse Acetylcholinesterase Inhibited by Tabun- Update

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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