Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Crystal structure of protoporphyrinogen IX oxidase: a key enzyme in haem and chlorophyll biosynthesis

Koch, Michael, Breithaupt, Constanze, Kiefersauer, Reiner, Freigang, Jörg, Huber, Robert and Messerschmidt, Albrecht 2004. Crystal structure of protoporphyrinogen IX oxidase: a key enzyme in haem and chlorophyll biosynthesis. EMBO Journal 23 (8) , pp. 1720-1728. 10.1038/sj.emboj.7600189

Full text not available from this repository.

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 α‐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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: European Molecular Biology Organization; Nature Publishing Group
ISSN: 0261-4189
Last Modified: 24 Jun 2017 11:00
URI: http://orca-mwe.cf.ac.uk/id/eprint/70167

Citation Data

Cited 129 times in Google Scholar. View in Google Scholar

Cited 149 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item