5hcu: Difference between revisions
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''' | ==Crystal structure of mouse acetylchoinesterase inhibited by DFP== | ||
<StructureSection load='5hcu' size='340' side='right' caption='[[5hcu]], [[Resolution|resolution]] 2.42Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5hcu]] is a 2 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5dtg 5dtg]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HCU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HCU FirstGlance]. <br> | |||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MIS:MONOISOPROPYLPHOSPHORYLSERINE'>MIS</scene></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=5hcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hcu OCA], [http://pdbe.org/5hcu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hcu RCSB], [http://www.ebi.ac.uk/pdbsum/5hcu PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://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;"> | |||
== Publication Abstract from PubMed == | |||
Acetylcholinesterase (AChE) that has been covalently inhibited by organophosphate compounds (OPCs), such as nerve agents and pesticides, has traditionally been reactivated by using nucleophilic oximes. There is, however, a clearly recognized need for new classes of compounds with the ability to reactivate inhibited AChE with improved in vivo efficacy. Here we describe our discovery of new functional groups-Mannich phenols and general bases-that are capable of reactivating OPC-inhibited AChE more efficiently than standard oximes and we describe the cooperative mechanism by which these functionalities are delivered to the active site. These discoveries, supported by preliminary in vivo results and crystallographic data, significantly broaden the available approaches for reactivation of AChE. | |||
Discovery of New Classes of Compounds that Reactivate Acetylcholinesterase Inhibited by Organophosphates.,Katz FS, Pecic S, Tran TH, Trakht I, Schneider L, Zhu Z, Ton-That L, Luzac M, Zlatanic V, Damera S, Macdonald J, Landry DW, Tong L, Stojanovic MN Chembiochem. 2015 Oct;16(15):2205-15. doi: 10.1002/cbic.201500348. Epub 2015 Sep , 9. PMID:26350723<ref>PMID:26350723</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5hcu" style="background-color:#fffaf0;"></div> | |||
== References == | |||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Acetylcholinesterase]] | |||
[[Category: Tong, L]] | [[Category: Tong, L]] | ||
[[Category: Tran, T H]] | |||
[[Category: Hydrolase]] | |||
Revision as of 19:52, 20 January 2016
Crystal structure of mouse acetylchoinesterase inhibited by DFPCrystal structure of mouse acetylchoinesterase inhibited by DFP
Structural highlights
Function[ACES_MOUSE] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Publication Abstract from PubMedAcetylcholinesterase (AChE) that has been covalently inhibited by organophosphate compounds (OPCs), such as nerve agents and pesticides, has traditionally been reactivated by using nucleophilic oximes. There is, however, a clearly recognized need for new classes of compounds with the ability to reactivate inhibited AChE with improved in vivo efficacy. Here we describe our discovery of new functional groups-Mannich phenols and general bases-that are capable of reactivating OPC-inhibited AChE more efficiently than standard oximes and we describe the cooperative mechanism by which these functionalities are delivered to the active site. These discoveries, supported by preliminary in vivo results and crystallographic data, significantly broaden the available approaches for reactivation of AChE. Discovery of New Classes of Compounds that Reactivate Acetylcholinesterase Inhibited by Organophosphates.,Katz FS, Pecic S, Tran TH, Trakht I, Schneider L, Zhu Z, Ton-That L, Luzac M, Zlatanic V, Damera S, Macdonald J, Landry DW, Tong L, Stojanovic MN Chembiochem. 2015 Oct;16(15):2205-15. doi: 10.1002/cbic.201500348. Epub 2015 Sep , 9. PMID:26350723[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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