Structural Insights into 3Fe-4S Ferredoxins Diversity in Highlighted by a First Redox Complex with P450

Overview

Journal Front Mol Biosci

Specialty Biology

Date 2023 Jan 26

PMID 36699703

Authors

Andrei Gilep

Tatsiana Varaksa

Sergey Bukhdruker

Anton Kavaleuski

Yury Ryzhykau

Sviatlana Smolskaya

Tatsiana Sushko

Kouhei Tsumoto

Irina Grabovec

Ivan Kapranov

Ivan Okhrimenko

Egor Marin

Mikhail Shevtsov

Alexey Mishin

Kirill Kovalev

Alexander Kuklin

Valentin Gordeliy

Leonid Kaluzhskiy

Oksana Gnedenko

Evgeniy Yablokov

Alexis Ivanov

Valentin Borshchevskiy

Natallia Strushkevich

Affiliations

Soon will be listed here.

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 -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.

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