2wg1: Difference between revisions
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<StructureSection load='2wg1' size='340' side='right'caption='[[2wg1]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='2wg1' size='340' side='right'caption='[[2wg1]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2wg1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2wg1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Tetronarce_californica Tetronarce californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WG1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WG1 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FP1:N-HYDROXY-1-(1-METHYLPYRIDIN-2(1H)-YLIDENE)METHANAMINE'>FP1</scene>, <scene name='pdbligand=GB:METHYLPHOSPHONIC+ACID+ESTER+GROUP'>GB</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FP1:N-HYDROXY-1-(1-METHYLPYRIDIN-2(1H)-YLIDENE)METHANAMINE'>FP1</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GB:METHYLPHOSPHONIC+ACID+ESTER+GROUP'>GB</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wg1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wg1 OCA], [https://pdbe.org/2wg1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wg1 RCSB], [https://www.ebi.ac.uk/pdbsum/2wg1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wg1 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wg1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wg1 OCA], [https://pdbe.org/2wg1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wg1 RCSB], [https://www.ebi.ac.uk/pdbsum/2wg1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wg1 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/ACES_TETCF ACES_TETCF] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions. | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
| Line 34: | Line 33: | ||
*[[Acetylcholinesterase|Acetylcholinesterase]] | *[[Acetylcholinesterase|Acetylcholinesterase]] | ||
*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]] | *[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]] | ||
*[[Sandbox AChE|Sandbox AChE]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Tetronarce californica]] | ||
[[Category: Ashani | [[Category: Ashani Y]] | ||
[[Category: Colletier | [[Category: Colletier JP]] | ||
[[Category: Froment | [[Category: Froment MT]] | ||
[[Category: Greenblatt | [[Category: Greenblatt HM]] | ||
[[Category: Masson | [[Category: Masson P]] | ||
[[Category: Nachon | [[Category: Nachon F]] | ||
[[Category: Sanson | [[Category: Sanson B]] | ||
[[Category: Silman | [[Category: Silman I]] | ||
[[Category: Sussman | [[Category: Sussman JL]] | ||
[[Category: Toker | [[Category: Toker L]] | ||
[[Category: Weik | [[Category: Weik M]] | ||
Latest revision as of 18:54, 13 December 2023
TERNARY COMPLEX OF THE AGED CONJUGATE OF TORPEDO CALIFORNICA ACEYLCHOLINESTERASE WITH SOMAN AND 2-PAMTERNARY COMPLEX OF THE AGED CONJUGATE OF TORPEDO CALIFORNICA ACEYLCHOLINESTERASE WITH SOMAN AND 2-PAM
Structural highlights
FunctionACES_TETCF Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions. 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 PubMedOrganophosphate compounds (OP) are potent inhibitors of acetylcholinesterases (AChEs) and can cause lethal poisoning in humans. Inhibition of AChEs by the OP soman involves phosphonylation of the catalytic serine, and subsequent dealkylation produces a form known as the "aged" enzyme. The nonaged form can be reactivated to a certain extent by nucleophiles, such as pralidoxime (2-PAM), whereas aged forms of OP-inhibited AChEs are totally resistant to reactivation. Here, we solved the X-ray crystal structures of AChE from Torpedo californica (TcAChE) conjugated with soman before and after aging. The absolute configuration of the soman stereoisomer adduct in the nonaged conjugate is P(S)C(R). A structural reorientation of the catalytic His440 side chain was observed during the aging process. Furthermore, the crystal structure of the ternary complex of the aged conjugate with 2-PAM revealed that the orientation of the oxime function does not permit nucleophilic attack on the phosphorus atom, thus providing a plausible explanation for its failure to reactivate the aged soman/AChE conjugate. Together, these three crystal structures provide an experimental basis for the design of new reactivators. Crystallographic Snapshots of Nonaged and Aged Conjugates of Soman with Acetylcholinesterase, and of a Ternary Complex of the Aged Conjugate with Pralidoxime (dagger).,Sanson B, Nachon F, Colletier JP, Froment MT, Toker L, Greenblatt HM, Sussman JL, Ashani Y, Masson P, Silman I, Weik M J Med Chem. 2009 Jul 30. PMID:19642642[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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