The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis.
Abstract
Human ferrochelatase (E.C. 4.99.1.1) is a homodimeric (86 kDa) mitochondrial membrane-associated enzyme that catalyzes the insertion of ferrous iron into protoporphyrin to form heme. We have determined the 2.0 A structure from the single wavelength iron anomalous scattering signal. The enzyme contains two NO-sensitive and uniquely coordinated [2Fe-2S] clusters. Its membrane association is mediated in part by a 12-residue hydrophobic lip that also forms the entrance to the active site pocket. The positioning of highly conserved residues in the active site in conjunction with previous biochemical studies support a catalytic model that may have significance in explaining the enzymatic defects that lead to the human inherited disease erythropoietic protoporphyria.
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Ferrochelatase (FECH), another rate-limiting enzyme, is responsible for insertion of Fe2+ into PpIX.
“Ferrochelatase (FECH), another rate-limiting enzyme, is responsible for insertion of Fe2+ into PpIX.”
From Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer (2011) · cites this paper as [26]
Conversion of PpIX to its downstream substrates requires the activity of rate-limiting enzyme ferrochelatase.
“Conversion of PpIX to its downstream substrates requires the activity of a rate-limiting enzyme ferrochelatase.”
From Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer (2011) · cites this paper as [26]
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- Authors
- Wu, C., Dailey, H. A., Rose, J. P., Burden, A. E., Sellers, V. M., & Wang, B.
- Affiliations
- University of Georgia (US)
- Corresponding author
- Bi‐Cheng Wang
- Venue
- Nature Structural Biology
- Published
- 2001-02-01
- Volume
- 8
- Issue
- 2
- Pages
- 156-160
- ISSN
- 1072-8368 (ISSN-L)
- OpenAlex
- W1932705370
- Cited by
- 227
- References
- 0
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 5 · 2023: 2 · 2022: 12 · 2021: 10 · 2020: 9 · 2019: 8 · 2018: 6 · 2017: 5 · 2016: 11 · 2015: 5 · 2014: 5 · 2013: 13 · 2012: 9
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Structural Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Georgia
- Georgia Research Alliance
- National Institute of Diabetes and Digestive and Kidney Diseases (R56DK032303)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- ferrochelatase, heme biosynthesis, protoporphyrin IX, [2Fe-2S] cluster, homodimeric enzyme, active site, erythropoietic protoporphyria, crystal structure
- MeSH terms
- Amino Acid Sequence, Binding Sites, Catalysis, Detergents, Ferrochelatase, Heme, Humans, Iron-Sulfur Proteins, Metals, Models, Molecular, Molecular Sequence Data, Mutation, Sequence Alignment, Protein Structure, Secondary, Crystallography, X-Ray, Dimerization
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