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Cited by 302Porphyrin Metabolism and DisordersPorphyrin and Phthalocyanine ChemistryEnzyme Structure and Function

The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.

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

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Koch, Michael, Breithaupt, Constanze, Kiefersauer, Reiner, Freigang, Jörg, Huber, Robert, Messerschmidt, Albrecht·2004·The EMBO Journal
DOI 10.1038/sj.emboj.7600189PMC PMC394243
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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.

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Crossref · 10.1038/sj.emboj.7600189

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Research works printed but not linked: 4

  1. Jones TA (1992) A, yaap, asap, @**?: a set of averaging programs. In Molecular Replacement (CCP4), Dodson EJ, Gover S, Wolf W (eds) pp 99–105. Warrington: Daresbury Laboratory
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  4. Nicholls A, Bharadwaj R, Honig B (1993) Grasp—graphical representation and analysis of surface‐properties. Biophys J 64: A166–A166

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Metadata

Authors
Koch, M., Breithaupt, C., Kiefersauer, R., Freigang, J., Huber, R., & Messerschmidt, A.
Affiliations
  • Max Planck Institute of Biochemistry (DE)
  • Bayer (Germany) (DE)
Corresponding author
  • Koch, Michael
  • Messerschmidt, Albrecht
ORCID
Venue
The EMBO Journal
Publisher
Springer Science and Business Media LLC
Published
2004-04-01
Volume
23
Issue
8
Pages
1720-1728
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
DOI
10.1038/sj.emboj.7600189
PMC
PMC394243
OpenAlex
W2064050113
Cited by
299
References
33
Citations by year
2026: 21 · 2025: 25 · 2024: 17 · 2023: 20 · 2022: 9 · 2021: 12 · 2020: 8 · 2019: 27 · 2018: 9 · 2017: 10 · 2016: 6 · 2015: 11 · 2014: 12 · 2013: 11 · 2012: 10
FWCI
3.44
Type
journal article
Language
en
Open access
Licence
Locations
  • The EMBO Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
Funders
  • European Synchrotron Radiation Facility
  • Bayer CropScience
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
  • Physical Sciences › Materials Science › Materials Chemistry › Porphyrin and Phthalocyanine Chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
Keywords
protoporphyrinogen IX oxidase, heme biosynthesis, chlorophyll biosynthesis, variegate porphyria, flavoprotein, FAD-binding domain, membrane-binding domain, ferrochelatase, herbicide targets, tobacco, crystal structure
MeSH terms
Amino Acid Sequence, Binding Sites, Catalysis, Cell Membrane, Chlorophyll, Ferrochelatase, Flavoproteins, Heme, Humans, Mitochondria, Models, Molecular, Molecular Sequence Data, Nicotiana, Sequence Alignment, Crystallography, X-Ray, Dimerization, Protein Structure, Quaternary, Protein Subunits, Mitochondrial Proteins, Oxidoreductases Acting on CH-CH Group Donors, Porphyria, Variegate, Protoporphyrinogen Oxidase

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