7TXE

Plasmodium falciparum Cyt c2 DSD

7TXE の概要

• エントリーDOI: 10.2210/pdb7txe/pdb
• 分子名称: Cytochrome c2, HEME C (3 entities in total)
• 機能のキーワード: alpha helix, heme, dsd, domain-swapped dimer, electron transport
• 由来する生物種: Plasmodium falciparum 3D7
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 37217.73

構造登録者

Hill, C.P.,Wienkers, H.J.,Whitby, F.G. (登録日: 2022-02-08, 公開日: 2023-05-10, 最終更新日: 2024-10-09)

主引用文献

Espino-Sanchez, T.J.,Wienkers, H.,Marvin, R.G.,Nalder, S.A.,Garcia-Guerrero, A.E.,VanNatta, P.E.,Jami-Alahmadi, Y.,Mixon Blackwell, A.,Whitby, F.G.,Wohlschlegel, J.A.,Kieber-Emmons, M.T.,Hill, C.P.,Sigala, P.A.
Direct tests of cytochrome c and c1 functions in the electron transport chain of malaria parasites
Proc Natl Acad Sci U S A, 120:e2301047120-, 2023

PubMed Abstract: The mitochondrial electron transport chain (ETC) of malaria parasites is a major antimalarial drug target, but critical cytochrome (cyt) functions remain unstudied and enigmatic. Parasites express two distinct cyt homologs ( and -2) with unusually sparse sequence identity and uncertain fitness contributions. cyt -2 is the most divergent eukaryotic cyt homolog currently known and has sequence features predicted to be incompatible with canonical ETC function. We tagged both cyt homologs and the related cyt for inducible knockdown. Translational repression of cyt and cyt was lethal to parasites, which died from ETC dysfunction and impaired ubiquinone recycling. In contrast, cyt -2 knockdown or knockout had little impact on blood-stage growth, indicating that parasites rely fully on the more conserved cyt for ETC function. Biochemical and structural studies revealed that both cyt and -2 are hemylated by holocytochrome synthase, but UV-vis absorbance and EPR spectra strongly suggest that cyt -2 has an unusually open active site in which heme is stably coordinated by only a single axial amino acid ligand and can bind exogenous small molecules. These studies provide a direct dissection of cytochrome functions in the ETC of malaria parasites and identify a highly divergent cytochrome with molecular adaptations that defy a conserved role in eukaryotic evolution.

PubMed: 37126705
DOI: 10.1073/pnas.2301047120

実験手法

X-RAY DIFFRACTION (2.3 Å)