7OPT

Crystal structure of Trypanosoma cruzi peroxidase

7OPT の概要

• エントリーDOI: 10.2210/pdb7opt/pdb
• 分子名称: Ascorbate peroxidase, PROTOPORPHYRIN IX CONTAINING FE, OXYGEN MOLECULE, ... (6 entities in total)
• 機能のキーワード: heme peroxidase, oxidoreductase
• 由来する生物種: Trypanosoma cruzi
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 74841.89

構造登録者

Freeman, S.L.,Kwon, H.,Skafar, V.,Fielding, A.J.,Martinez, A.,Piacenza, L.,Radi, R.,Raven, E.L. (登録日: 2021-06-01, 公開日: 2022-06-08, 最終更新日: 2024-01-31)

主引用文献

Freeman, S.L.,Skafar, V.,Kwon, H.,Fielding, A.J.,Moody, P.C.E.,Martinez, A.,Issoglio, F.M.,Inchausti, L.,Smircich, P.,Zeida, A.,Piacenza, L.,Radi, R.,Raven, E.L.
Crystal structure of Trypanosoma cruzi heme peroxidase and characterization of its substrate specificity and compound I intermediate.
J.Biol.Chem., 298:102204-102204, 2022

PubMed Abstract: The protozoan parasite Trypanosoma cruzi is the causative agent of American trypanosomiasis, otherwise known as Chagas disease. To survive in the host, the T. cruzi parasite needs antioxidant defense systems. One of these is a hybrid heme peroxidase, the T. cruzi ascorbate peroxidase-cytochrome c peroxidase enzyme (TcAPx-CcP). TcAPx-CcP has high sequence identity to members of the class I peroxidase family, notably ascorbate peroxidase (APX) and cytochrome c peroxidase (CcP), as well as a mitochondrial peroxidase from Leishmania major (LmP). The aim of this work was to solve the structure and examine the reactivity of the TcAPx-CcP enzyme. Low temperature electron paramagnetic resonance spectra support the formation of an exchange-coupled [Fe(IV)=O Trp] compound I radical species, analogous to that used in CcP and LmP. We demonstrate that TcAPx-CcP is similar in overall structure to APX and CcP, but there are differences in the substrate-binding regions. Furthermore, the electron transfer pathway from cytochrome c to the heme in CcP and LmP is preserved in the TcAPx-CcP structure. Integration of steady state kinetic experiments, molecular dynamic simulations, and bioinformatic analyses indicates that TcAPx-CcP preferentially oxidizes cytochrome c but is still competent for oxidization of ascorbate. The results reveal that TcAPx-CcP is a credible cytochrome c peroxidase, which can also bind and use ascorbate in host cells, where concentrations are in the millimolar range. Thus, kinetically and functionally TcAPx-CcP can be considered a hybrid peroxidase.

PubMed: 35772495
DOI: 10.1016/j.jbc.2022.102204

実験手法

X-RAY DIFFRACTION (2.02 Å)