Approaches for increasing the electrocatalitic efficiency of cytochrome P450 3A4

Shumyantseva, Victoria V.; Koroleva, P. I.; Булко, Т. В.; Shkel, Tatsiana; Gilep, Andrei A.; Veselovsky, A. V.

doi:10.1016/j.bioelechem.2022.108277

Cited by 11 publications

(16 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Earlier, the electrochemical properties of the hemeprotein CYP3A4 immobilized on the screen-printed graphite electrode modified with the synthetic lipid-like compound DDAB were investigated, in detail, in both anaerobic and aerobic conditions [ 16 , 17 , 18 ]. For the enhancement in catalytic activity and surface coverage of the electrode with the hemeprotein, we propose the use of a composite of DDAB and the pore-forming bacterial toxin streptolysin O (SLO).…”

Section: Resultsmentioning

confidence: 99%

“…Improvements in cytochrome P450 electrocatalysis remain a significant challenge. Various approaches have been proposed for the creation of electrochemical systems that retain and increase the catalytic activity of the enzymes [ 6 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Moreover, enzyme immobilization in a volume-confined environment could increase its stability and reduce denaturation and protein unfolding [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Improving the Efficiency of Electrocatalysis of Cytochrome P450 3A4 by Modifying the Electrode with Membrane Protein Streptolysin O for Studying the Metabolic Transformations of Drugs

et al. 2023

Self Cite

View full text Add to dashboard Cite

In the present work, screen-printed electrodes (SPE) modified with a synthetic surfactant, didodecyldimethylammonium bromide (DDAB) and streptolysin O (SLO) were prepared for cytochrome P450 3A4 (CYP3A4) immobilization, direct non-catalytic and catalytic electrochemistry. The immobilized CYP3A4 demonstrated a pair of redox peaks with a formal potential of −0.325 ± 0.024 V (vs. the Ag/AgCl reference electrode). The electron transfer process showed a surface-controlled mechanism (“protein film voltammetry”) with an electron transfer rate constant (ks) of 0.203 ± 0.038 s−1. Electrochemical CYP3A4-mediated reaction of N-demethylation of erythromycin was explored with the following parameters: an applied potential of −0.5 V and a duration time of 20 min. The system with DDAB/SLO as the electrode modifier showed conversion of erythromycin with an efficiency higher than the electrode modified with DDAB only. Confining CYP3A4 inside the protein frame of SLO accelerated the enzymatic reaction. The increases in product formation in the reaction of the electrochemical N-demethylation of erythromycin for SPE/DDAB/CYP3A4 and SPE/DDAB/SLO/CYP3A4 were equal to 100 ± 22% and 297 ± 7%, respectively. As revealed by AFM images, the SPE/DDAB/SLO possessed a more developed surface with protein cavities in comparison with SPE/DDAB for the effective immobilization of the CYP3A4 enzyme.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Improving the Efficiency of Electrocatalysis of Cytochrome P450 3A4 by Modifying the Electrode with Membrane Protein Streptolysin O for Studying the Metabolic Transformations of Drugs

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Struktur yang dihasilkan mengidentifikasi mode pengikatan asam lemak karboksilat yang berbeda dari yang disarankan oleh struktur BM3 [10]. Perbandingan struktur CYP2E1 baru ini dengan struktur yang memiliki molekul kecil di situs aktif menunjukkan akomodasi struktural yang diperlukan untuk memfasilitasi pengikatan CYP2E1 dari dua kelas senyawa yang berbeda [11]. Pengikatan asam lemak dalam enzim sitokrom P450 terbatas pada enzim bakteri terlarut BM3 (CYP102A1), P450 BioI (CYP107H), dan P450BS (CYP152A1).…”

Section: Hasil Dan Pembahasanunclassified

Pengujian Pakis Kinca (Nephrolepis Cordifolia (L) C. Presl) Sebagai Inhibitor enzyim sitokrom sub time 2E1 Dengan Metode Doking

Rahmadani,

Agustin,

Samsul Hadi

2024

JFM

View full text Add to dashboard Cite

CYP450 adalah enzim yang terlibat dalam monooksigenasi beragam senyawa asing dan endogen. Dari 57 enzim manusia, mungkin sepertiga bertanggung jawab metabolisme xenobiotik, termasuk obat-obatan. Penelitian ini menggunakan metode docking untuk melihat potensi senyawa yang terkandung dari Nephrolepis Cordifolia sebagai inhibitor CYP2E1. Doking yang dilakukan menggunkan senyawa yang terkandung dari Nephrolepis Cordifolia. Metode yang digunakan dalam docking adalah rigid docking menggunakan software autodock4. Analisis data yang digunakan adalah adanya ikatan hidrogen dan enrgy Gibbs. Hasil dari penelitian ini yaitu energi terendah adalah β-sitosterol dengan energi Gibbs -8.233 kcal/mol. Ikatan yang terbentuk adalah ikatan hidrofob. benzyl butyl phthalate, β-ionone, oleanolic acid terjadiny ikatan hidrofob. Myristic acid membentuk ikatan hidrogen dengan HIS 109. Eugenol membentuk ikatan hidrogen dengan THR303. Kesimpulan senyawa yang berpotensi sebagai inhibitor CYP2E1 adalah Myristic acid dan Eugenol.

show abstract

“…Нами был предложен подход, при котором первой стадией электрокатализа была не стадия восстановления иона железа гема, а именно стадия образования фермент-субстратного комплекса для дальнейшей продуктивной работы системы. Предварительная инкубация CYP 3А4, нековалентно иммобилизованного на электроде за счет включения в матрицу ДДАБ с субстратом (антибиотиком группы макролидов эритромицином) до стадии получения электронов, положительно влияла на каталитические функции фермента [32]. Выход продукта реакции N-деметилирования эритромицина -формальдегида, возрос в 1.46 раза, а максимальная скорость реакции увеличилась с 9.21 × 10 -11 M/мин до 1.40 × 10 -10 M/мин.…”

Section: каталитический механизм функционирования Cyp как основа для ...unclassified

“…Флавиновые нуклеотиды являются кофакторами редуктаз -белков редокс-партнеров CYP -и, соответственно, посредниками в передаче электронов между восстановительным эквивалентом NADPH и CYP, согласно общепринятой схеме электронного транспорта (рис. 4) [32]. Для моделирования классической электрон-транспортной схемы на электроде были использованы различные подходы, основанные на образовании комплексов или на включении флавиновых кофакторов или флавинсодержащих доменов в структуру CYP в роли диффузионных медиаторов переноса электронов.…”

Section: флавиновые нуклеотиды как диффузионные медиаторы переноса эл...unclassified

Comparative Analysis of Bioelectrocatalytic Cytochrome P450 3A4 Systems

Koroleva,

Shumyantseva

2024

BMCRM

View full text Add to dashboard Cite

This article describes the approaches developed by the authors with the aim to increase the efficiency of electro enzymatic reactions catalyzed by cytochrome P450 3A4. A comparative analysis of cytochrome P450 3A4 systems was carried out during the formation of the functional complexes hemoprotein-flavin nucleotides as low-molecular models of NAD(P)H-dependent cytochrome P450 reductase. The formation of a productive enzyme-substrate complex before the stage ofaccepting electrons from the modified electrode was studied from the electocatalytic viewpoint. Incorporation of the enzyme into nanopores of different nature on the electrode (2D-3D transition) was also studied. The results on the electrochemical reduction of bactosomes as the functionally active models of the microsomal monooxygenase system are also considered. The electrochemical and electrocatalytic parameters of cytochrome P450 3A4 were compared for different models of the electrocatalytic generation of metabolites.

show abstract

Approaches for increasing the electrocatalitic efficiency of cytochrome P450 3A4

Cited by 11 publications

References 59 publications

Improving the Efficiency of Electrocatalysis of Cytochrome P450 3A4 by Modifying the Electrode with Membrane Protein Streptolysin O for Studying the Metabolic Transformations of Drugs

Improving the Efficiency of Electrocatalysis of Cytochrome P450 3A4 by Modifying the Electrode with Membrane Protein Streptolysin O for Studying the Metabolic Transformations of Drugs

Pengujian Pakis Kinca (Nephrolepis Cordifolia (L) C. Presl) Sebagai Inhibitor enzyim sitokrom sub time 2E1 Dengan Metode Doking

Comparative Analysis of Bioelectrocatalytic Cytochrome P450 3A4 Systems

Contact Info

Product

Resources

About