5DTI

Crystal structure of mouse acetylcholinesterase

Summary for 5DTI

• Entry DOI: 10.2210/pdb5dti/pdb
• Related: 5DTG 5DTJ
• Descriptor: Acetylcholinesterase (2 entities in total)
• Functional Keywords: hydrolase
• Biological source: Mus musculus (Mouse)
• Cellular location: Cell junction, synapse. Isoform H: Cell membrane; Lipid-anchor, GPI- anchor; Extracellular side: P21836
• Total number of polymer chains: 2
• Total formula weight: 120013.57

Authors

Tran, T.H.,Tong, L. (deposition date: 2015-09-18, release date: 2015-10-21, Last modification date: 2024-11-20)

Primary citation

Katz, F.S.,Pecic, S.,Tran, T.H.,Trakht, I.,Schneider, L.,Zhu, Z.,Ton-That, L.,Luzac, M.,Zlatanic, V.,Damera, S.,Macdonald, J.,Landry, D.W.,Tong, L.,Stojanovic, M.N.
Discovery of New Classes of Compounds that Reactivate Acetylcholinesterase Inhibited by Organophosphates.
Chembiochem, 16:2205-2215, 2015

PubMed Abstract: 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.

PubMed: 26350723
DOI: 10.1002/cbic.201500348

Experimental method

X-RAY DIFFRACTION (2.003 Å)