Correlation Engine 2.0
Clear Search sequence regions


  • CYP2C9 (12)
  • drug reactions (1)
  • flavodoxin (7)
  • haem (1)
  • oxygen (1)
  • redox (2)
  • responses drugs (1)
  • Sizes of these terms reflect their relevance to your search.

    Polymorphism is an important aspect in drug metabolism responsible for different individual response to drug dosage, often leading to adverse drug reactions. Here human CYP2C9 as well as its polymorphic variants CYP2C9*2 and CYP2C9*3 present in approximately 35% of the Caucasian population have been engineered by linking their gene to the one of D. vulgaris flavodoxin (FLD) that acts as regulator of the electron flow from the electrode surface to the haem. The redox properties of the immobilised proteins were investigated by cyclic voltammetry and electrocatalysis was measured in presence of the largely used anticoagulant drug S-warfarin, marker substrate for CYP2C9. Immobilisation of the CYP2C9-FLD, CYP2C9*2-FLD and CYP2C9*3-FLD on DDAB modified glassy carbon electrodes showed well defined redox couples on the oxygen-free cyclic voltammograms and mid-point potentials of all enzymes were calculated. Electrocatalysis in presence of substrate and quantification of the product formed showed lower catalytic activities for the CYP2C9*3-FLD (2.73 ± 1.07 min-1) and CYP2C9*2-FLD (12.42 ± 2.17 min-1) compared to the wild type CYP2C9-FLD (18.23 ± 1.29 min-1). These differences in activity among the CYP2C9 variants are in line with the reported literature data, and this set the basis for the use of the bio-electrode for the measurement of the different catalytic responses towards drugs very relevant in therapy. Copyright © 2020 Elsevier B.V. All rights reserved.

    Citation

    Paola Panicco, Silvia Castrignanò, Sheila J Sadeghi, Giovanna Di Nardo, Gianfranco Gilardi. Engineered human CYP2C9 and its main polymorphic variants for bioelectrochemical measurements of catalytic response. Bioelectrochemistry (Amsterdam, Netherlands). 2021 Apr;138:107729


    PMID: 33421896

    View Full Text