Adrenodoxins and Their Role in the Cytochrome P450 Systems

IF 0.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
V. V. Shumyantseva, T. V. Bulko, O. V. Gnedenko, E. O. Yablokov, S. A. Usanov, A. S. Ivanov
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Abstract

The role of partner proteins in the formation of functional complexes in cytochrome P450 systems was investigated by means of the optical biosensor technique, used to determine kinetic constants and equilibrium dissociation constants of complexes of cytochrome CYP11A1 (P450scc) with wild-type adrenodoxin (Adx WT) and mutant forms of adrenodoxin R106D and D109R. Wild-type adrenodoxin (Kd = (1.23 ± 0.09) × 10–6 M) and mutant D109R (Kd = (2.37 ± 0.09) × 10–8 M) formed complexes with cytochrome P450scc. In the case of the R106D mutant, no complex formation was detected. The possibility of participation of adrenodoxins and their mutant variants in the process of electron transfer as electron donors in mitochondrial cytochrome P450 systems, was assessed studying the electrochemical properties of these iron-sulfur proteins Adx WT and mutant forms of adrenodoxins. Adx WT, mutant forms R106D and D109R have redox potentials E1/2 significantly more negative than cytochromes P450 (–579 ± 10 mV, –590 ± 15 mV, and –528 ± 10 mV, respectively). These results suggest that Adx WT and mutant forms may be electron donors in the cytochrome P450 systems.

Abstract Image

肾上腺素及其在细胞色素P450系统中的作用
摘要/ abstract摘要:利用光学生物传感器技术研究了细胞色素CYP11A1 (P450scc)与野生型肾上腺素还毒素(Adx WT)和突变型肾上腺素还毒素R106D和D109R配合物的动力学常数和平衡解离常数,研究了配对蛋白在细胞色素P450系统中功能复合物形成中的作用。野生型肾上腺素(Kd =(1.23±0.09)× 10-6 M)和突变型D109R (Kd =(2.37±0.09)× 10-8 M)与细胞色素P450scc形成复合物。在R106D突变体的情况下,没有检测到复杂的形成。通过研究这些铁硫蛋白Adx WT和肾上腺素突变体的电化学性质,评估了肾上腺素及其突变体在线粒体细胞色素P450系统中作为电子供体参与电子转移过程的可能性。与细胞色素P450相比,突变型R106D和D109R的氧化还原电位e2 /2显著负(分别为-579±10 mV、-590±15 mV和-528±10 mV)。这些结果表明,Adx WT和突变体可能是细胞色素P450系统中的电子供体。
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来源期刊
CiteScore
1.10
自引率
0.00%
发文量
31
期刊介绍: Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry   covers all major aspects of biomedical chemistry and related areas, including proteomics and molecular biology of (patho)physiological processes, biochemistry, neurochemistry, immunochemistry and clinical chemistry, bioinformatics, gene therapy, drug design and delivery, biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine. The journal also publishes review articles. All issues of the journal usually contain solicited reviews.
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