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HutW from Vibrio cholerae Is an Anaerobic Heme-Degrading Enzyme with Unique Functional Properties
Open accessAbstract
Increasing antibiotic resistance, and a growing recognition of the importance of the human microbiome, demand that new therapeutic targets be identified. Characterization of metabolic pathways that are unique to enteric pathogens represents a promising approach. Iron is often the rate-limiting factor for growth, and Vibrio cholerae, the causative agent of cholera, has been shown to contain numerous genes that function in the acquisition of iron from the environment. Included in this arsenal of genes are operons dedicated to obtaining iron from heme and heme-containing proteins. Given the persistence of cholera, an important outstanding question is whether V. cholerae is capable of anaerobic heme degradation as was recently reported for enterohemorrhagic Escherichia coli O157:H7. In this work, we demonstrate that HutW from V. cholerae is a radical S -adenosylmethionine methyl transferase involved in the anaerobic opening of the porphyrin ring of heme. However, in contrast to the enzyme ChuW, found in enterohemorrhagic E. coli O157:H7, there are notable differences in the mechanism and products of the HutW reaction. Of particular interest are data that demonstrate HutW will catalyze ring opening as well as tetrapyrrole reduction and can utilize reduced nicotinamide adenine dinucleotide phosphate as an electron source. The biochemical and biophysical properties of HutW are presented, and the evolutionary implications are discussed.
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“Haem oxygenases are classified into five different enzyme families including the HO-1 family, the IsdG family, ChuZ, ChuW and HutW 31,32 .”
From Nutritional immunity: the battle for nutrient metals at the host–pathogen interface (2022) · cites this paper as [32]
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Metadata
- Authors
- Brimberry, M., Toma, M. A., Hines, K. M., & Lanzilotta, W. N.
- Affiliations
- University of Georgia (US)
- Corresponding author
- Lanzilotta, William N.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-02-18
- Volume
- 60
- Issue
- 9
- Pages
- 699-710
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- PMC
- PMC8672366
- OpenAlex
- W3131325509
- Cited by
- 19
- References
- 54
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 2
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM124203)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Keywords
- Vibrio cholerae, iron acquisition, enteric pathogens, enzyme evolution
- MeSH terms
- Anaerobiosis, Bacterial Outer Membrane Proteins, Heme, Methyltransferases, NADP, Protein Conformation, S-Adenosylmethionine, Vibrio cholerae, Gene Expression Regulation, Bacterial, Tetrapyrroles
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