4b80: Difference between revisions
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<StructureSection load='4b80' size='340' side='right'caption='[[4b80]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='4b80' size='340' side='right'caption='[[4b80]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4b80]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4b80]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B80 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B80 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A36:N-[2-(DIETHYLAMINO)ETHYL]-1-(4-FLUOROPHENYL)METHANESULFONAMIDE'>A36</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P4C:O-ACETALDEHYDYL-HEXAETHYLENE+GLYCOL'>P4C</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.5Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A36:N-[2-(DIETHYLAMINO)ETHYL]-1-(4-FLUOROPHENYL)METHANESULFONAMIDE'>A36</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P4C:O-ACETALDEHYDYL-HEXAETHYLENE+GLYCOL'>P4C</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4b80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b80 OCA], [https://pdbe.org/4b80 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b80 RCSB], [https://www.ebi.ac.uk/pdbsum/4b80 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b80 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/ACES_MOUSE ACES_MOUSE] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 27: | Line 26: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Akfur | [[Category: Akfur C]] | ||
[[Category: Allgardsson | [[Category: Allgardsson A]] | ||
[[Category: Andersson | [[Category: Andersson CD]] | ||
[[Category: Berg | [[Category: Berg L]] | ||
[[Category: Ekstrom | [[Category: Ekstrom F]] | ||
[[Category: Forsgren | [[Category: Forsgren N]] | ||
[[Category: Linusson | [[Category: Linusson A]] | ||
[[Category: Qian | [[Category: Qian W]] | ||
Latest revision as of 14:45, 20 December 2023
Mus musculus Acetylcholinesterase in complex with N-(2-Diethylamino-ethyl)-1-(4-fluoro-phenyl)-methanesulfonamideMus musculus Acetylcholinesterase in complex with N-(2-Diethylamino-ethyl)-1-(4-fluoro-phenyl)-methanesulfonamide
Structural highlights
FunctionACES_MOUSE Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Publication Abstract from PubMedThe molecular interactions between the enzyme acetylcholinesterase (AChE) and two compound classes consisting of N-[2-(diethylamino)-ethyl]-benzenesulfonamides and N-[2-(diethylamino)-ethyl]-benzenemethanesulfonamides have been investigated using organic synthesis, enzymatic assays, X-ray crystallography, and thermodynamic profiling. The inhibitors' aromatic properties were varied to establish structure-activity relationships (SAR) between the inhibitors and the peripheral anionic site (PAS) of AChE. The two structurally similar compound classes proved to have distinctly divergent SARs in terms of their inhibition capacity of AChE. Eight X-ray structures revealed that the two sets have different conformations in PAS. Furthermore, thermodynamic profiles of the binding between compounds and AChE revealed class-dependent differences of the entropy/enthalpy contributions to the free energy of binding. Further development of the entropy-favored compound class resulted in the synthesis of the most potent inhibitor, and an extension beyond the established SARs. The divergent SARs will be utilized to develop reversible inhibitors of AChE into reactivators of nerve agent inhibited AChE. Divergent Structure-Activity Relationships of Structurally Similar Acetylcholinesterase Inhibitors.,Andersson CD, Forsgren N, Akfur C, Allgardsson A, Berg L, Engdahl C, Qian W, Ekstrom FJ, Linusson A J Med Chem. 2013 Aug 28. PMID:23984975[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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