TY - JOUR
T1 - Structural insights into 3Fe–4S ferredoxins diversity in M. tuberculosis highlighted by a first redox complex with P450
AU - Gilep, Andrei
AU - Varaksa, Tatsiana
AU - Bukhdruker, Sergey
AU - Kavaleuski, Anton
AU - Ryzhykau, Yury
AU - Smolskaya, Sviatlana
AU - Sushko, Tatsiana
AU - Tsumoto, Kouhei
AU - Grabovec, Irina
AU - Kapranov, Ivan
AU - Okhrimenko, Ivan
AU - Marin, Egor
AU - Shevtsov, Mikhail
AU - Mishin, Alexey
AU - Kovalev, Kirill
AU - Kuklin, Alexander
AU - Gordeliy, Valentin
AU - Kaluzhskiy, Leonid
AU - Gnedenko, Oksana
AU - Yablokov, Evgeniy
AU - Ivanov, Alexis
AU - Borshchevskiy, Valentin
AU - Strushkevich, Natallia
N1 - Publisher Copyright:
Copyright © 2023 Gilep, Varaksa, Bukhdruker, Kavaleuski, Ryzhykau, Smolskaya, Sushko, Tsumoto, Grabovec, Kapranov, Okhrimenko, Marin, Shevtsov, Mishin, Kovalev, Kuklin, Gordeliy, Kaluzhskiy, Gnedenko, Yablokov, Ivanov, Borshchevskiy and Strushkevich.
PY - 2023/1/9
Y1 - 2023/1/9
N2 - 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.
AB - 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.
KW - 3Fe–4S ferredoxins
KW - crystal structure
KW - cytochrome P450
KW - protein–protein interactions
KW - redox complex
UR - http://www.scopus.com/inward/record.url?scp=85146910435&partnerID=8YFLogxK
U2 - 10.3389/fmolb.2022.1100032
DO - 10.3389/fmolb.2022.1100032
M3 - Article
C2 - 36699703
AN - SCOPUS:85146910435
SN - 2296-889X
VL - 9
JO - Frontiers in Molecular Biosciences
JF - Frontiers in Molecular Biosciences
M1 - 1100032
ER -
