1cfj: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==METHYLPHOSPHONYLATED ACETYLCHOLINESTERASE (AGED) OBTAINED BY REACTION WITH O-ISOPROPYLMETHYLPHOSPHONOFLUORIDATE (GB, SARIN)== | ==METHYLPHOSPHONYLATED ACETYLCHOLINESTERASE (AGED) OBTAINED BY REACTION WITH O-ISOPROPYLMETHYLPHOSPHONOFLUORIDATE (GB, SARIN)== | ||
<StructureSection load='1cfj' size='340' side='right' caption='[[1cfj]], [[Resolution|resolution]] 2.60Å' scene=''> | <StructureSection load='1cfj' size='340' side='right'caption='[[1cfj]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1cfj]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1cfj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Torpedo_californica Torpedo californica]. The June 2004 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Acetylcholinesterase'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2004_6 10.2210/rcsb_pdb/mom_2004_6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CFJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CFJ FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GB:METHYLPHOSPHONIC+ACID+ESTER+GROUP'>GB</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GB:METHYLPHOSPHONIC+ACID+ESTER+GROUP'>GB</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase], with EC number [https://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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1cfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cfj OCA], [https://pdbe.org/1cfj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cfj RCSB], [https://www.ebi.ac.uk/pdbsum/1cfj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cfj ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/ACES_TORCA ACES_TORCA]] 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]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cf/1cfj_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cf/1cfj_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
| Line 31: | Line 31: | ||
==See Also== | ==See Also== | ||
*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]] | *[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 41: | Line 37: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Acetylcholinesterase]] | [[Category: Acetylcholinesterase]] | ||
[[Category: Large Structures]] | |||
[[Category: RCSB PDB Molecule of the Month]] | [[Category: RCSB PDB Molecule of the Month]] | ||
[[Category: Torpedo californica]] | [[Category: Torpedo californica]] | ||
Revision as of 18:09, 2 June 2021
METHYLPHOSPHONYLATED ACETYLCHOLINESTERASE (AGED) OBTAINED BY REACTION WITH O-ISOPROPYLMETHYLPHOSPHONOFLUORIDATE (GB, SARIN)METHYLPHOSPHONYLATED ACETYLCHOLINESTERASE (AGED) OBTAINED BY REACTION WITH O-ISOPROPYLMETHYLPHOSPHONOFLUORIDATE (GB, SARIN)
Structural highlights
Function[ACES_TORCA] 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 PubMedOrganophosphorus acid anhydride (OP) nerve agents are potent inhibitors which rapidly phosphonylate acetylcholinesterase (AChE) and then may undergo an internal dealkylation reaction (called "aging") to produce an OP-enzyme conjugate that cannot be reactivated. To understand the basis for irreversible inhibition, we solved the structures of aged conjugates obtained by reaction of Torpedo californica AChE (TcAChE) with diisopropylphosphorofluoridate (DFP), O-isopropylmethylphosponofluoridate (sarin), or O-pinacolylmethylphosphonofluoridate (soman) by X-ray crystallography to 2.3, 2.6, or 2.2 A resolution, respectively. The highest positive difference density peak corresponded to the OP phosphorus and was located within covalent bonding distance of the active-site serine (S200) in each structure. The OP-oxygen atoms were within hydrogen-bonding distance of four potential donors from catalytic subsites of the enzyme, suggesting that electrostatic forces significantly stabilize the aged enzyme. The active sites of aged sarin- and soman-TcAChE were essentially identical and provided structural models for the negatively charged, tetrahedral intermediate that occurs during deacylation with the natural substrate, acetylcholine. Phosphorylation with DFP caused an unexpected movement in the main chain of a loop that includes residues F288 and F290 of the TcAChE acyl pocket. This is the first major conformational change reported in the active site of any AChE-ligand complex, and it offers a structural explanation for the substrate selectivity of AChE. Crystal structures of aged phosphonylated acetylcholinesterase: nerve agent reaction products at the atomic level.,Millard CB, Kryger G, Ordentlich A, Greenblatt HM, Harel M, Raves ML, Segall Y, Barak D, Shafferman A, Silman I, Sussman JL Biochemistry. 1999 Jun 1;38(22):7032-9. PMID:10353814[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||