1SEZ

Crystal Structure of Protoporphyrinogen IX Oxidase

Summary for 1SEZ

• Entry DOI: 10.2210/pdb1sez/pdb
• Descriptor: Protoporphyrinogen oxidase, mitochondrial, FLAVIN-ADENINE DINUCLEOTIDE, 4-BROMO-3-(5'-CARBOXY-4'-CHLORO-2'-FLUOROPHENYL)-1-METHYL-5-TRIFLUOROMETHYL-PYRAZOL, ... (5 entities in total)
• Functional Keywords: fad-binding, para-hydroxy-benzoate-hydroxylase fold (phbh-fold), monotopic membrane-binding domain, oxidoreductase
• Biological source: Nicotiana tabacum (common tobacco)
• Cellular location: Mitochondrion: O24164
• Total number of polymer chains: 2
• Total formula weight: 114767.22

Authors

Koch, M.,Breithaupt, C.,Kiefersauer, R.,Freigang, J.,Huber, R.,Messerschmidt, A. (deposition date: 2004-02-19, release date: 2004-04-13, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.9 Å)