Artursson_2009_Toxicology_265_108

Reference

Title : Reactivation of tabun-hAChE investigated by structurally analogous oximes and mutagenesis - Artursson_2009_Toxicology_265_108
Author(s) : Artursson E , Akfur C , Hornberg A , Worek F , Ekstrom F
Ref : Toxicology , 265 :108 , 2009
Abstract : The nerve agent tabun inhibits the essential enzyme acetylcholinesterase (AChE) by a rapid phosphoramidation of the catalytic serine residue. Oximes, such as K027 and HLo-7, can reactivate tabun-inhibited human AChE (tabun-hAChE) whereas the activity of their close structural analogue HI-6 is notably low. To investigate HI-6, K027 and HLo-7, residues lining the active-site gorge of hAChE were substituted and the effects on kinetic parameters for reactivation were determined. None of the mutants (Asp74Asn, Asp74Glu, Tyr124Phe, Tyr337Ala, Tyr337Phe, Phe338Val and Tyr341Ala) were able to facilitate HI-6-mediated reactivation of tabun-hAChE. In contrast, Tyr124Phe and Tyr337Phe induce a 2-2.5-fold enhancement of the bimolecular rate constant for K027 and HLo-7. The largest effects on the dissociation constant (3.5-fold increase) and rate constant (20-fold decrease) were observed for Tyr341Ala and Asp74Asn, respectively. These findings demonstrate the importance of residues located distant from the conjugate during the reactivation of tabun-hAChE.
ESTHER : Artursson_2009_Toxicology_265_108
PubMedSearch : Artursson_2009_Toxicology_265_108
PubMedID: 19761810

Citations formats

Artursson E, Akfur C, Hornberg A, Worek F, Ekstrom F (2009)
Reactivation of tabun-hAChE investigated by structurally analogous oximes and mutagenesis
Toxicology 265 :108

Artursson E, Akfur C, Hornberg A, Worek F, Ekstrom F (2009)
Toxicology 265 :108

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    [id] => 36124
    [paper] => Artursson_2009_Toxicology_265_108
    [author] => Artursson E || Akfur C || Hornberg A || Worek F || Ekstrom F
    [year] => 2009
    [title] => Reactivation of tabun-hAChE investigated by structurally analogous oximes and mutagenesis
    [journal] => Toxicology
    [volume] => 265
    [page] => 108
    [medline] => 19761810
    [abstract] => Artursson_2009_Toxicology_265_108
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            [longtext] => Artursson_2009_Toxicology_265_108
            [content] => The nerve agent tabun inhibits the essential enzyme acetylcholinesterase (AChE) by a rapid phosphoramidation of the catalytic serine residue. Oximes, such as K027 and HLo-7, can reactivate tabun-inhibited human AChE (tabun-hAChE) whereas the activity of their close structural analogue HI-6 is notably low. To investigate HI-6, K027 and HLo-7, residues lining the active-site gorge of hAChE were substituted and the effects on kinetic parameters for reactivation were determined. None of the mutants (Asp74Asn, Asp74Glu, Tyr124Phe, Tyr337Ala, Tyr337Phe, Phe338Val and Tyr341Ala) were able to facilitate HI-6-mediated reactivation of tabun-hAChE. In contrast, Tyr124Phe and Tyr337Phe induce a 2-2.5-fold enhancement of the bimolecular rate constant for K027 and HLo-7. The largest effects on the dissociation constant (3.5-fold increase) and rate constant (20-fold decrease) were observed for Tyr341Ala and Asp74Asn, respectively. These findings demonstrate the importance of residues located distant from the conjugate during the reactivation of tabun-hAChE.
        )

)