The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
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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Cites
Reduced stress defense in heme oxygenase 1-deficient cells
Poss, K. D., & Tonegawa, S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.20.10925 · Cited by 1,294
Bacterial Iron Sources: From Siderophores to Hemophores
Wandersman, C., & Delepelaire, P. (2004) · Annual Review of Microbiology · doi:10.1146/annurev.micro.58.030603.123811 · Cited by 930
In silico fragmentation for computer assisted identification of metabolite mass spectra
Wolf, S., Schmidt, S., Müller-Hannemann, M., & Neumann, S. (2010) · BMC Bioinformatics · doi:10.1186/1471-2105-11-148 · Cited by 698
Studies on the Chemical Nature of Clostridial Ferredoxin
Lovenberg, W. M., Buchanan, B. B., & Rabinowitz, J. C. (1963) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)51805-6 · Cited by 599
Mayhew, S. G. (1978) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1978.tb12269.x · Cited by 534
Purification and characterization of biliverdin reductase from rat liver.
Kutty, R. K., & Maines, M. D. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)69552-9 · Cited by 297
IsdG and IsdI, Heme-degrading Enzymes in the Cytoplasm of Staphylococcus aureus
Skaar, E. P., Gaspar, A. H., & Schneewind, O. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m307952200 · Cited by 282
Wilks, A., & de Montellano, P. R. O. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41536-0 · Cited by 253
Emerging strategies in microbial haem capture
Genco, C. A., & Dixon, D. W. (2001) · Molecular Microbiology · doi:10.1046/j.1365-2958.2001.02231.x · Cited by 242
Schmitt, M. P. (1997) · Journal of Bacteriology · doi:10.1128/jb.179.3.838-845.1997 · Cited by 234
Research works printed but not linked: 2
- 10.1016/s0021-9258(18)41536-0 · DOI
- 10.1073/pnas.0504289102 · DOI · Paper page
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Nutritional immunity: the battle for nutrient metals at the host–pathogen interface
Murdoch, C. C., & Skaar, E. P. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00745-6 · Cited by 701
Functional Diversity of HemN-like Proteins
Cheng, J., Liu, W., Zhu, X., & Zhang, Q. (2022) · ACS Bio & Med Chem Au · doi:10.1021/acsbiomedchemau.1c00058 · Cited by 25
Heme in Bacterial Pathogenesis and as an Antimicrobial Target
Chen, P., & Skaar, E. P. (2025) · Chemical Reviews · doi:10.1021/acs.chemrev.5c00528 · Cited by 21
Making and breaking carbon-carbon bonds in class C radical SAM methyltransferases
Brimberry, M., Mathew, L., & Lanzilotta, W. N. (2021) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2021.111636 · Cited by 14
Self-citationWan, Q., Zhai, S., Wang, Y., Xu, M. J., Chen, M., & Guo, S. (2024) · Journal of Fish Diseases · doi:10.1111/jfd.13931 · Cited by 11
Class C Radical SAM Methyltransferases Involved in Anaerobic Heme Degradation
Mathew, L., Brimberry, M., & Lanzilotta, W. N. (2021) · ACS Bio & Med Chem Au · doi:10.1021/acsbiomedchemau.1c00047 · Cited by 10
Self-citationEvidence for Porphyrin-Mediated Electron Transfer in the Radical SAM Enzyme HutW
Brimberry, M., Corrigan, P. S., Silakov, A., & Lanzilotta, W. N. (2023) · Biochemistry · doi:10.1021/acs.biochem.2c00474 · Cited by 8
Self-citationRadical SAM‐Dependent Demetallation of Heme
Cheng, J., Ding, W., & Zhang, Q. (2022) · Chinese Journal of Chemistry · doi:10.1002/cjoc.202200032 · Cited by 7
Srivastava, S., Gupta, A. K., & Gupta, P. (2025) · Journal of Water Process Engineering · doi:10.1016/j.jwpe.2025.107881 · Cited by 6
Brunson, D. N., Manzer, H. S., Smith, A. B., Zackular, J. P., Kitten, T. O., & Lemos, J. A. C. (2025) · mBio · doi:10.1128/mbio.00146-25 · Cited by 4
HutZ from Aliivibrio fischeri Inhibits HutW-Mediated Anaerobilin Formation by Sequestering Heme
McGregor, A. K., & Wolthers, K. R. (2024) · Biochemistry · doi:10.1021/acs.biochem.4c00624 · Cited by 3
Heme utilization by the enterococci
Brunson, D. N., & Lemos, J. A. C. (2024) · FEMS Microbes · doi:10.1093/femsmc/xtae019 · Cited by 3
A dye-decolorizing peroxidase from Vibrio cholerae can demetallate heme
Uchida, T., Umetsu, S., Sasaki, M., Yoshimura, H., Omura, I., & Ishimori, K. (2024) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2024.112764 · Cited by 2
Mechanisms of bacterial heme uptake and degradation: Diverse strategies for ring opening
Johnson, K., Xue, F., & Wilks, A. (2025) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2025.113023 · Cited by 2
Rahmawaty, A., Cheng, L., Hsu, J., Maekawa, S., Wang, P., & Chen, S. (2025) · Journal of Fish Diseases · doi:10.1111/jfd.70036 · Cited by 1
Harnessing the Versatility of SAM‐Dependent Enzymes: From Mechanism to Application
Zhao, Y., Meng, S., Chen, M., Xu, S., Wang, J., Xu, G., & Cui, H. (2026) · ChemBioChem · doi:10.1002/cbic.70416 · Cited by 1
Characterization of a Heme-Binding Radical SAM Enzyme HemW from Moraxella catarrhalis
Padgett, C. M., Bollmeyer, M. M., Boswinkle, K., Iavarone, A. T., de Crécy‐Lagard, V., Britt, R. D., & Zhu, W. (2026) · ACS Bio & Med Chem Au · doi:10.1021/acsbiomedchemau.6c00111
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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