The IsdG‐family of haem oxygenases degrades haem to a novel chromophore
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Summary: Enzymatic haem catabolism by haem oxygenases is conserved from bacteria to humans and proceeds through a common mechanism leading to the formation of iron, carbon monoxide and biliverdin. The first members of a novel class of haem oxygenases were recently identified in Staphylococcus aureus (IsdG and IsdI) and were termed the IsdG‐family of haem oxygenases. Enzymes of the IsdG‐family form tertiary structures distinct from those of the canonical haem oxygenase family, suggesting that IsdG‐family members degrade haem via a unique reaction mechanism. Herein we report that the IsdG‐family of haem oxygenases degrade haem to the oxo‐bilirubin chromophore staphylobilin. We also present the crystal structure of haem‐bound IsdI in which haem ruffling and constrained binding of oxygen is consistent with cleavage of the porphyrin ring at the β‐ or δ‐ meso carbons. Combined, these data establish that the IsdG‐family of haem oxygenases degrades haem to a novel chromophore distinct from biliverdin.
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IsdG and IsdI degrade heme to iron and a novel chromophore, staphylobilin, unlike human heme-oxygenases which produce biliverdin.
“Unlike human heme-oxygenases which degrade heme to iron and the chromophore biliverdin, IsdG and IsdI degrade heme to iron and a novel chromophore, staphylobilin [104].”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [104]
IsdG and IsdI degrade heme to a mixture of beta- and sigma-isomers of oxo-bilirubin, collectively called staphylobilin.
“Heme degradation catalyzed by the IsdG-family of heme oxygenases results in the production of a mixture of β- and σ-isomers of oxo-bilirubin, molecules collectively referred to as staphylobilin (Fig. 1B) (64).”
From Molecular Mechanisms of <i>Staphylococcus aureus</i> Iron Acquisition (2011) · cites this paper as [64]
IsdG and IsdI are structurally similar and are the first described members of the Isd heme oxygenase family, which catabolizes heme to staphylobilin instead of biliverdin.
“IsdG and IsdI are structurally similar and are the first described members of the Isd heme oxygenase family, which catabolizes heme to staphylobilin instead of biliverdin [117–119].”
From Heme Synthesis and Acquisition in Bacterial Pathogens (2016) · cites this paper as [117]
Membrane-localized IsdE allows heme to enter the cytoplasm, where IsdG and IsdI degrade heme to release iron and form staphylobilin.
“Membrane-localized IsdE allows for heme passage into the cytoplasm, where heme is degraded by the heme oxygenases IsdG and IsdI to liberate iron and form staphylobilin [15, 20 -26].”
From IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus (2014) · cites this paper as [24]
IsdG and IsdI convert heme into staphylobilin, a yellow oxo-bilirubin molecule.
“In contrast, IsdG and IsdI degrade heme to the yellow oxo-bilirubin molecule known as staphylobilin [49].”
From A battle for iron: host sequestration and Staphylococcus aureus acquisition (2012) · cites this paper as [49]
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Self-citation
- Authors
- Reniere, M. L., Ukpabi, G. N., Harry, S. R., Stec, D. F., Krull, R., Wright, D. W., Bachmann, B. O., Murphy, M. E., & Skaar, E. P.
- Affiliations
- Vanderbilt University Medical Center (US)
- University of British Columbia (CA)
- Bruker (United States) (US)
- Corresponding author
- Skaar, Eric P.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2010-03
- Volume
- 75
- Issue
- 6
- Pages
- 1529-1538
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- PMC
- PMC3800195
- OpenAlex
- W2119635659
- Cited by
- 139
- References
- 30
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 8 · 2020: 6 · 2019: 16 · 2018: 9 · 2017: 9 · 2016: 14 · 2015: 11 · 2014: 10 · 2013: 12 · 2012: 8
- FWCI
- 4.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Vanderbilt University
- Canadian Light Source
- University of Saskatchewan
- Searle Scholars Program
- National Institutes of Health
- U.S. Public Health Service
- Canadian Institutes of Health Research (MOP-49597)
- Natural Sciences and Engineering Research Council of Canada
- National Heart, Lung, and Blood Institute (T32HL007751, 5 T32HL07751)
- National Institute of Allergy and Infectious Diseases (AI073843, AI69233, R01AI069233, R01AI073843)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Keywords
- Staphylococcus aureus, biliverdin, crystal structure, enzyme mechanism
- MeSH terms
- Bacterial Proteins, Heme, Heme Oxygenase (Decyclizing), Mixed Function Oxygenases, Models, Molecular, Oxidation-Reduction, Oxygenases, Staphylococcus aureus, Molecular Structure, Protein Structure, Tertiary, Crystallography, X-Ray
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