Maintenance window scheduled to begin at February 14th 2200 est. until 0400 est. February 15th

(e.g. yourname@email.com)

Forgot Password?

    Defense Visual Information Distribution Service Logo

    Defeating Deadly Attacks to the Central Nervous System

    hAChE Phosphonylated by Aged Soman

    Courtesy Photo | Active site gorge of hAChE phosphonylated by aged soman. The figure was made from a...... read more read more

    FORT BELOVIR, VIRGINIA, UNITED STATES

    07.25.2016

    Courtesy Story

    Defense Threat Reduction Agency's Chemical and Biological Technologies Department

    Fort Belvoir, Va. If an adversary wanted to stop an army in its tracks, a chemical and biological weapon designed to incapacitate the central nervous system (CNS) would be devastating to our warfighters. With this in mind, the Defense Threat Reduction Agency’s Joint Science and Technology Office and the French company CEA are diligently trying to improve existing medical countermeasures (MCMs) by using acetylcholinesterase, or AChE, a key enzyme in the nervous system, to defend against such threats.

    Understanding the chemical nature of organophosphate deactivation of human acetylcholinesterase (hAChE) in detail allows advancement of improved medical countermeasures for the protection and treatment of affected warfighters.

    JSTO and CEA are exploring the effects of non-covalent reversible and covalent irreversible inhibitors and recently published a study on the molecular dynamic effects of these inhibitors on hAChE.

    Scientists from CEA performed molecular dynamics studies on inhibited forms of AChE to examine the effects of inhibition on protein structure. The AChE was treated with the nerve agent soman to form the covalent and aged adduct. This subsequently underwent analysis called incoherent neutron scattering to investigate the molecular dynamics at the picosecond-nanosecond timescale and examine the non-covalent and covalent inhibitors. Results showed decreased flexibility of the inhibited protein attributed to reordering of water molecules within the structure.

    Conversely, AChE treated with Huperzine A, a reversible, non-covalent inhibitor, showed little to no effect in structural flexibility when compared to untreated proteins. Thus, several additive contributions seem responsible for the stiffening effect of the soman inhibition rather than a single interaction.

    The study, published in the Physical Chemistry Chemical Physics, “Dynamics of human acetylcholinesterase bound to non-covalent and covalent inhibitors shedding light on changes to the water network structure,” offers scientists a better understanding of the chemical nature of organophosphate hAChE.

    This research will play an instrumental role in developing medical countermeasures for warfighters exposed to deadly nerve agents.

    POC: Dr. Peter Falk; peter.m.falk.civ@mail.mil

    NEWS INFO

    Date Taken: 07.25.2016
    Date Posted: 07.25.2016 14:46
    Story ID: 204955
    Location: FORT BELOVIR, VIRGINIA, US

    Web Views: 504
    Downloads: 0

    PUBLIC DOMAIN