7A9A

Crystal structure of rubredoxin B (Rv3250c) from Mycobacterium tuberculosis

7A9A の概要

• エントリーDOI: 10.2210/pdb7a9a/pdb
• 分子名称: Rubredoxin, FE (III) ION, ZINC ION, ... (8 entities in total)
• 機能のキーワード: electron transport, iron sulfur, metalloprotein, cytochrome p450 redox partner, cyp, cyp124, cyp125, cyp142
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 58497.35

構造登録者

Vakhrameev, D.,Kavaleuski, A.,Bukhdruker, S.,Marin, E.,Sushko, T.,Grabovec, I.P.,Gilep, A.,Strushkevich, N.,Borshchevskiy, V. (登録日: 2020-09-01, 公開日: 2021-03-03, 最終更新日: 2024-01-31)

主引用文献

Sushko, T.,Kavaleuski, A.,Grabovec, I.,Kavaleuskaya, A.,Vakhrameev, D.,Bukhdruker, S.,Marin, E.,Kuzikov, A.,Masamrekh, R.,Shumyantseva, V.,Tsumoto, K.,Borshchevskiy, V.,Gilep, A.,Strushkevich, N.
A new twist of rubredoxin function in M. tuberculosis.
Bioorg.Chem., 109:104721-104721, 2021

PubMed Abstract: Electron transfer mediated by metalloproteins drives many biological processes. Rubredoxins are a ubiquitous [1Fe-0S] class of electron carriers that play an important role in bacterial adaptation to changing environmental conditions. In Mycobacterium tuberculosis, oxidative and acidic stresses as well as iron starvation induce rubredoxins expression. However, their functions during M. tuberculosis infection are unknown. In the present work, we show that rubredoxin B (RubB) is able to efficiently shuttle electrons from cognate reductases, FprA and FdR to support catalytic activity of cytochrome P450s, CYP124, CYP125, and CYP142, which are important for bacterial viability and pathogenicity. We solved the crystal structure of RubB and characterized the interaction between RubB and CYPs using site-directed mutagenesis. Mutations that not only neutralize single charge but also change the specific residues on the surface of RubB did not dramatically decrease activity of studied CYPs. Together with isothermal calorimetry (ITC) experiments, the obtained results suggest that interactions are transient and not highly specific. The redox potential of RubB is -264 mV vs. Ag/AgCl and the measured extinction coefficients are 9931 Mcm and 8371 Mcm at 380 nm and 490 nm, respectively. Characteristic parameters of RubB along with the discovered function might be useful for biotechnological applications. Our findings suggest that a switch from ferredoxins to rubredoxins might be crucial for M. tuberculosis to support CYPs activity during the infection.

PubMed: 33618255
DOI: 10.1016/j.bioorg.2021.104721

実験手法

X-RAY DIFFRACTION (1.17 Å)