ArticleBiochemistry2007
Direct measurement of metal ion chelation in the active site of human ferrochelatase.
Article in Biochemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Applications of the Whole-Cell System in the Efficient Biosynthesis of Heme.International journal of molecular sciences · 2023Review
- New Avenues of Heme Synthesis Regulation.International journal of molecular sciences · 2022Review
- Ferrochelatase: Mapping the Intersection of Iron and Porphyrin Metabolism in the Mitochondria.Frontiers in cell and developmental biology · 2022Review
- Mitochondrial contact site and cristae organizing system (MICOS) machinery supports heme biosynthesis by enabling optimal performance of ferrochelatase.Redox biology · 2021Article
- Insight into the function of active site residues in the catalytic mechanism of human ferrochelatase.The Biochemical journal · 2021Article
- The active site of magnesium chelatase.Nature plants · 2020Article
- Review
- Handling heme: The mechanisms underlying the movement of heme within and between cells.Free radical biology & medicine · 2019Review
- Ferrochelatase π-helix: Implications from examining the role of the conserved π-helix glutamates in porphyrin metalation and product release.Archives of biochemistry and biophysics · 2018Article
- Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product.Microbiology and molecular biology reviews : MMBR · 2017Review
- A Novel Role for Progesterone Receptor Membrane Component 1 (PGRMC1): A Partner and Regulator of Ferrochelatase.Biochemistry · 2016Article
- Article
- Investigation by MD simulation of the key residues related to substrate-binding and heme-release in human ferrochelatase.Journal of molecular modeling · 2013Article
- Erythroid heme biosynthesis and its disorders.Cold Spring Harbor perspectives in medicine · 2013Review
- One ring to rule them all: trafficking of heme and heme synthesis intermediates in the metazoans.Biochimica et biophysica acta · 2012Review
- Identification and characterization of solvent-filled channels in human ferrochelatase.Biochemistry · 2012Article
- Nickel(II) chelatase variants directly evolved from murine ferrochelatase: porphyrin distortion and kinetic mechanism.Biochemistry · 2011Article
- Bacterial ferrochelatase turns human: Tyr13 determines the apparent metal specificity of Bacillus subtilis ferrochelatase.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2011Article
- FERROCHELATASE: THE CONVERGENCE OF THE PORPHYRIN BIOSYNTHESIS AND IRON TRANSPORT PATHWAYS.Journal of porphyrins and phthalocyanines · 2011Article
- Identification and characterization of an inhibitory metal ion-binding site in ferrochelatase.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The final step in heme biosynthesis, insertion of ferrous iron into protoporphyrin IX, is catalyzed by protoporphyrin IX ferrochelatase (EC 4.99.1.1). We demonstrate that pre-steady state human ferrochelatase (R115L) exhibits a stoichiometric burst of product formation and substrate consumption, consistent with a rate-determining step following metal ion chelation. Detailed analysis shows that chelation requires at least two steps, rapid binding followed by a slower (k approximately 1 s-1) irreversible step, provisionally assigned to metal ion chelation. Comparison with steady state data reveals that the rate-determining step in the overall reaction, conversion of free porphyrin to free metalloporphyrin, occurs after chelation and is most probably product release. We have measured rate constants for significant steps on the enzyme and demonstrate that metal ion chelation, with a rate constant of 0.96 s-1, is approximately 10 times faster than the rate-determining step in the steady state (kcat = 0.1 s-1). The effect of an additional E343D mutation is apparent at multiple stages in the reaction cycle with a 7-fold decrease in kcat and a 3-fold decrease in kchel. This conservative mutation primarily affects events occurring after metal ion chelation. Further evaluation of structure-function data on site-directed mutants will therefore require both steady state and pre-steady state approaches.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.