Frontiers in Molecular Biosciences (Jan 2023)
Structural insights into 3Fe–4S ferredoxins diversity in M. tuberculosis highlighted by a first redox complex with P450
- Andrei Gilep,
- Andrei Gilep,
- Tatsiana Varaksa,
- Sergey Bukhdruker,
- Anton Kavaleuski,
- Yury Ryzhykau,
- Yury Ryzhykau,
- Sviatlana Smolskaya,
- Tatsiana Sushko,
- Kouhei Tsumoto,
- Kouhei Tsumoto,
- Irina Grabovec,
- Ivan Kapranov,
- Ivan Okhrimenko,
- Egor Marin,
- Mikhail Shevtsov,
- Alexey Mishin,
- Kirill Kovalev,
- Alexander Kuklin,
- Alexander Kuklin,
- Valentin Gordeliy,
- Leonid Kaluzhskiy,
- Oksana Gnedenko,
- Evgeniy Yablokov,
- Alexis Ivanov,
- Valentin Borshchevskiy,
- Valentin Borshchevskiy,
- Natallia Strushkevich
Affiliations
- Andrei Gilep
- Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus
- Andrei Gilep
- Laboratory of Intermolecular Interactions, Institute of Biomedical Chemistry, Moscow, Russia
- Tatsiana Varaksa
- Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus
- Sergey Bukhdruker
- Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
- Anton Kavaleuski
- Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus
- Yury Ryzhykau
- Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
- Yury Ryzhykau
- Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Dubna, Russia
- Sviatlana Smolskaya
- Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus
- Tatsiana Sushko
- Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, Japan
- Kouhei Tsumoto
- Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, Japan
- Kouhei Tsumoto
- Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Irina Grabovec
- Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus
- Ivan Kapranov
- Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
- Ivan Okhrimenko
- Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
- Egor Marin
- Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
- Mikhail Shevtsov
- Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
- Alexey Mishin
- Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
- Kirill Kovalev
- European Molecular Biology Laboratory, Hamburg Unit C/O DESY, Hamburg, Germany
- Alexander Kuklin
- Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
- Alexander Kuklin
- Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Dubna, Russia
- Valentin Gordeliy
- Institute of Crystallography, University of Aachen (RWTH), Aachen, Germany
- Leonid Kaluzhskiy
- Laboratory of Intermolecular Interactions, Institute of Biomedical Chemistry, Moscow, Russia
- Oksana Gnedenko
- Laboratory of Intermolecular Interactions, Institute of Biomedical Chemistry, Moscow, Russia
- Evgeniy Yablokov
- Laboratory of Intermolecular Interactions, Institute of Biomedical Chemistry, Moscow, Russia
- Alexis Ivanov
- Laboratory of Intermolecular Interactions, Institute of Biomedical Chemistry, Moscow, Russia
- Valentin Borshchevskiy
- Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
- Valentin Borshchevskiy
- Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Dubna, Russia
- Natallia Strushkevich
- Skolkovo Institute of Science and Technology, Moscow, Russia
- DOI
- https://doi.org/10.3389/fmolb.2022.1100032
- Journal volume & issue
-
Vol. 9
Abstract
Ferredoxins are small iron–sulfur proteins and key players in essential metabolic pathways. Among all types, 3Fe–4S ferredoxins are less studied mostly due to anaerobic requirements. Their complexes with cytochrome P450 redox partners have not been structurally characterized. In the present work, we solved the structures of both 3Fe–4S ferredoxins from M. tuberculosis—Fdx alone and the fusion FdxE–CYP143. Our SPR analysis demonstrated a high-affinity binding of FdxE to CYP143. According to SAXS data, the same complex is present in solution. The structure reveals extended multipoint interactions and the shape/charge complementarity of redox partners. Furthermore, FdxE binding induced conformational changes in CYP143 as evident from the solved CYP143 structure alone. The comparison of FdxE–CYP143 and modeled Fdx–CYP51 complexes further revealed the specificity of ferredoxins. Our results illuminate the diversity of electron transfer complexes for the production of different secondary metabolites.
Keywords
