ArticleBiochemistry2007
Altered orientation of active site residues in variants of human ferrochelatase. Evidence for a hydrogen bond network involved in catalysis.
Article in Biochemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Milestones in the Elucidation of Heme Biosynthesis.Chemical reviews · 2026Review
- Nickel-chelatase activity of SirB variants mimicking the His arrangement in the naturally occurring nickel-chelatase CfbA.FEBS open bio · 2024Article
- 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 antenna-like domain of the cyanobacterial ferrochelatase can bind chlorophyll and carotenoids in an energy-dissipative configuration.The Journal of biological chemistry · 2019Article
- Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product.Microbiology and molecular biology reviews : MMBR · 2017Review
- Article
- HemQ: An iron-coproporphyrin oxidative decarboxylase for protoheme synthesis in Firmicutes and Actinobacteria.Archives of biochemistry and biophysics · 2015Review
- Investigation by MD simulation of the key residues related to substrate-binding and heme-release in human ferrochelatase.Journal of molecular modeling · 2013Article
- A conserved amphipathic ligand binding region influences k-path-dependent activity of cytochrome C oxidase.Biochemistry · 2013Article
- 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
- Heme biosynthesis and its regulation: towards understanding and improvement of heme biosynthesis in filamentous fungi.Applied microbiology and biotechnology · 2011Review
- FERROCHELATASE: THE CONVERGENCE OF THE PORPHYRIN BIOSYNTHESIS AND IRON TRANSPORT PATHWAYS.Journal of porphyrins and phthalocyanines · 2011Article
- Product release rather than chelation determines metal specificity for ferrochelatase.Journal of molecular biology · 2009Article
- Molecular dynamics simulations of mouse ferrochelatase variants: what distorts and orientates the porphyrin?Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2009Article
- A pi-helix switch selective for porphyrin deprotonation and product release in human ferrochelatase.Journal of molecular biology · 2007Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Ferrochelatase catalyzes the terminal step in heme biosynthesis, the insertion of ferrous iron into protoporphyrin to form protoheme IX. The crystal structures of human ferrochelatase both with and without the protoporphyrin substrate bound have been determined previously. The substrate-free enzyme has an open active site pocket, while in the substrate-bound enzyme, the active site pocket is closed around the porphyrin macrocycle and a number of active site residues have reoriented side chains. To understand how and why these structural changes occur, we have substituted three amino acid residues (H263, H341, and F337) whose side chains occupy different spatial positions in the substrate-free versus substrate-bound ferrochelatases. The catalytic and structural properties of ferrochelatases containing the amino acid substitutions H263C, H341C, and F337A were examined. It was found that in the H263C and H341C variants, but not the F337A variant enzymes, the side chains of N75, M76, R164, H263, F337, H341, and E343 are oriented in a fashion similar to what is found in ferrochelatase with the bound porphyrin substrate. However, all of the variant forms possess open active site pockets which are found in the structure of porphyrin-free ferrochelatase. Thus, while the interior walls of the active site pocket are remodeled in these variants, the exterior lips remain unaltered in position. One possible explanation for this collective reorganization of active site side chains is the presence of a hydrogen bond network among H263, H341, and E343. This network is disrupted in the variants by alteration of H263C or H341C. In the substrate-bound enzyme, the formation of a hydrogen bond between H263 and a pyrrole nitrogen results in disruption of the network. The possible role of this network in catalysis is discussed.
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