6NEA

Human Acetylcholinesterase in complex with reactivator, HLo7

Summary for 6NEA

• Entry DOI: 10.2210/pdb6nea/pdb
• Descriptor: Acetylcholinesterase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 121746.94

Authors

Bester, S.M.,McGuire, J.,Height, J.J.,Pegan, S.D. (deposition date: 2018-12-17, release date: 2019-06-12, Last modification date: 2024-10-23)

Primary citation

Hsu, F.L.,Bae, S.Y.,McGuire, J.,Anderson, D.R.,Bester, S.M.,Height, J.J.,Pegan, S.D.,Walz, A.J.
Synthesis and Molecular Properties of Nerve Agent Reactivator HLo-7 Dimethanesulfonate.
Acs Med.Chem.Lett., 10:761-766, 2019

PubMed Abstract: The threat of a deliberate release of chemical nerve agents has underscored the need to continually improve field effective treatments for these types of poisonings. The oxime containing HLö-7 is a potential second-generation therapeutic reactivator. A synthetic process for HLö-7 is detailed with improvements to the DIBAL reduction and ion exchange steps. HLö-7 was visualized for the first time within the active site of human acetylcholinesterase and its relative potency confirmed against various nerve agents using a phrenic nerve hemidiaphragm assay.

PubMed: 31097996
DOI: 10.1021/acsmedchemlett.9b00021

Experimental method

X-RAY DIFFRACTION (2.419 Å)