1SEZ

Crystal Structure of Protoporphyrinogen IX Oxidase

1SEZ の概要

• エントリーDOI: 10.2210/pdb1sez/pdb
• 分子名称: Protoporphyrinogen oxidase, mitochondrial, FLAVIN-ADENINE DINUCLEOTIDE, 4-BROMO-3-(5'-CARBOXY-4'-CHLORO-2'-FLUOROPHENYL)-1-METHYL-5-TRIFLUOROMETHYL-PYRAZOL, ... (5 entities in total)
• 機能のキーワード: fad-binding, para-hydroxy-benzoate-hydroxylase fold (phbh-fold), monotopic membrane-binding domain, oxidoreductase
• 由来する生物種: Nicotiana tabacum (common tobacco)
• 細胞内の位置: Mitochondrion: O24164
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 114767.22

構造登録者

Koch, M.,Breithaupt, C.,Kiefersauer, R.,Freigang, J.,Huber, R.,Messerschmidt, A. (登録日: 2004-02-19, 公開日: 2004-04-13, 最終更新日: 2024-10-30)

主引用文献

Koch, M.,Breithaupt, C.,Kiefersauer, R.,Freigang, J.,Huber, R.,Messerschmidt, A.
Crystal structure of protoporphyrinogen IX oxidase: a key enzyme in haem and chlorophyll biosynthesis.
Embo J., 23:1720-1728, 2004

PubMed Abstract: Protoporphyrinogen IX oxidase (PPO), the last common enzyme of haem and chlorophyll biosynthesis, catalyses the oxidation of protoporphyrinogen IX to protoporphyrin IX. The membrane-embedded flavoprotein is the target of a large class of herbicides. In humans, a defect in PPO is responsible for the dominantly inherited disease variegate porphyria. Here we present the crystal structure of mitochondrial PPO from tobacco complexed with a phenyl-pyrazol inhibitor. PPO forms a loosely associated dimer and folds into an FAD-binding domain of the p-hydroxybenzoate-hydrolase fold and a substrate-binding domain that enclose a narrow active site cavity beneath the FAD and an alpha-helical membrane-binding domain. The active site architecture suggests a specific substrate-binding mode compatible with the unusual six-electron oxidation. The membrane-binding domains can be docked onto the dimeric structure of human ferrochelatase, the next enzyme in haem biosynthesis, embedded in the opposite side of the membrane. This modelled transmembrane complex provides a structural explanation for the uncoupling of haem biosynthesis observed in variegate porphyria patients and in plants after inhibiting PPO.

PubMed: 15057273
DOI: 10.1038/sj.emboj.7600189

実験手法

X-RAY DIFFRACTION (2.9 Å)