Catalytic activity and stereoselectivity of engineered phosphotriesterases towards structurally different nerve agents in vitro.
Bispecific bioscavenger
Detoxification
Mutant
Nerve agent
PASylation
Phosphotriesterase
Journal
Archives of toxicology
ISSN: 1432-0738
Titre abrégé: Arch Toxicol
Pays: Germany
ID NLM: 0417615
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
07
05
2021
accepted:
15
06
2021
pubmed:
24
6
2021
medline:
12
1
2022
entrez:
23
6
2021
Statut:
ppublish
Résumé
Highly toxic organophosphorus nerve agents, especially the extremely stable and persistent V-type agents such as VX, still pose a threat to the human population and require effective medical countermeasures. Engineered mutants of the Brevundimonas diminuta phosphotriesterase (BdPTE) exhibit enhanced catalytic activities and have demonstrated detoxification in animal models, however, substrate specificity and fast plasma clearance limit their medical applicability. To allow better assessment of their substrate profiles, we have thoroughly investigated the catalytic efficacies of five BdPTE mutants with 17 different nerve agents using an AChE inhibition assay. In addition, we studied one BdPTE version that was fused with structurally disordered PAS polypeptides to enable delayed plasma clearance and one bispecific BdPTE with broadened substrate spectrum composed of two functionally distinct subunits connected by a PAS linker. Measured k
Identifiants
pubmed: 34160649
doi: 10.1007/s00204-021-03094-0
pii: 10.1007/s00204-021-03094-0
pmc: PMC8298220
doi:
Substances chimiques
Nerve Agents
0
Phosphoric Triester Hydrolases
EC 3.1.8.-
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2815-2823Informations de copyright
© 2021. The Author(s).
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