4b80: Difference between revisions
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==Mus musculus Acetylcholinesterase in complex with N-(2-Diethylamino-ethyl)-1-(4-fluoro-phenyl)-methanesulfonamide== | |||
<StructureSection load='4b80' size='340' side='right' caption='[[4b80]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4b80]] is a 2 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4B80 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1c2b|1c2b]], [[1c2o|1c2o]], [[1j06|1j06]], [[1j07|1j07]], [[1ku6|1ku6]], [[1maa|1maa]], [[1mah|1mah]], [[1n5m|1n5m]], [[1n5r|1n5r]], [[1q83|1q83]], [[1q84|1q84]], [[2c0p|2c0p]], [[2c0q|2c0q]], [[2h9y|2h9y]], [[2ha0|2ha0]], [[2ha2|2ha2]], [[2ha3|2ha3]], [[2ha4|2ha4]], [[2ha5|2ha5]], [[2ha6|2ha6]], [[2ha7|2ha7]], [[2jey|2jey]], [[2jez|2jez]], [[2jf0|2jf0]], [[2jge|2jge]], [[2jgf|2jgf]], [[2jgg|2jgg]], [[2jgh|2jgh]], [[2jgi|2jgi]], [[2jgj|2jgj]], [[2jgk|2jgk]], [[2jgl|2jgl]], [[2jgm|2jgm]], [[2whp|2whp]], [[2whq|2whq]], [[2whr|2whr]], [[2wls|2wls]], [[2wu3|2wu3]], [[2wu4|2wu4]], [[2xud|2xud]], [[2xuf|2xuf]], [[2xug|2xug]], [[2xuh|2xuh]], [[2xui|2xui]], [[2xuj|2xuj]], [[2xuk|2xuk]], [[2xuo|2xuo]], [[2xup|2xup]], [[2xuq|2xuq]], [[4a16|4a16]], [[4a23|4a23]], [[4ara|4ara]], [[4arb|4arb]], [[4b7z|4b7z]], [[4b81|4b81]], [[4b82|4b82]], [[4b83|4b83]], [[4b84|4b84]], [[4b85|4b85]]</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=4b80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b80 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4b80 RCSB], [http://www.ebi.ac.uk/pdbsum/4b80 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The 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<ref>PMID:23984975</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== | ==See Also== | ||
*[[Acetylcholinesterase|Acetylcholinesterase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Acetylcholinesterase]] | [[Category: Acetylcholinesterase]] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Akfur, C | [[Category: Akfur, C]] | ||
[[Category: Allgardsson, A | [[Category: Allgardsson, A]] | ||
[[Category: Andersson, C D | [[Category: Andersson, C D]] | ||
[[Category: Berg, L | [[Category: Berg, L]] | ||
[[Category: Ekstrom, F | [[Category: Ekstrom, F]] | ||
[[Category: Forsgren, N | [[Category: Forsgren, N]] | ||
[[Category: Linusson, A | [[Category: Linusson, A]] | ||
[[Category: Qian, W | [[Category: Qian, W]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Inhibitor]] | [[Category: Inhibitor]] | ||