Structural insights into the mechanism of oxidative activation of heme-free H-NOX from Vibrio cholerae
Abstract
Bacterial heme nitric oxide/oxygen (H-NOX) domains are nitric oxide (NO) or oxygen sensors. This activity is mediated through binding of the ligand to a heme cofactor. However, H-NOX from Vibrio cholerae (Vc H-NOX) can be easily purified in a heme-free state that is capable of reversibly responding to oxidation, suggesting a heme-independent function as a redox sensor. This occurs by oxidation of Cys residues at a zinc-binding site conserved in a subset of H-NOX homologs. Remarkably, zinc is not lost from the protein upon oxidation, although its ligation environment is significantly altered. Using a combination of computational and experimental approaches, we have characterized localized structural changes that accompany the formation of specific disulfide bonds between Cys residues upon oxidation. Furthermore, the larger-scale structural changes accompanying oxidation appear to mimic those changes observed upon NO binding to the heme-bound form. Thus, Vc H-NOX and its homologs may act as both redox and NO sensors by completely separate mechanisms.
- Authors:
-
- New Mexico State Univ., Las Cruces, NM (United States). Dept. of Chemistry and Biochemistry
- Reed College, Portland, OR (United States). Dept. of Chemistry
- New Mexico State Univ., Las Cruces, NM (United States). Dept. of Plant and Environmental Sciences
- Publication Date:
- Research Org.:
- SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1624989
- Grant/Contract Number:
- AC02-76SF00515
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Biochemical Journal
- Additional Journal Information:
- Journal Volume: 477; Journal Issue: 6; Journal ID: ISSN 0264-6021
- Publisher:
- Biochemical Society
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Biochemistry & Molecular Biology; disulphide bonds; redox signalling; zinc; Computational Biology; Molecular Bases of Health & Disease; Signaling
Citation Formats
Mukhopadhyay, Roma, Chacón, Kelly N., Jarvis, Jacqueline M., Talipov, Marat R., and Yukl, Erik T.. Structural insights into the mechanism of oxidative activation of heme-free H-NOX from Vibrio cholerae. United States: N. p., 2020.
Web. doi:10.1042/bcj20200124.
Mukhopadhyay, Roma, Chacón, Kelly N., Jarvis, Jacqueline M., Talipov, Marat R., & Yukl, Erik T.. Structural insights into the mechanism of oxidative activation of heme-free H-NOX from Vibrio cholerae. United States. https://doi.org/10.1042/bcj20200124
Mukhopadhyay, Roma, Chacón, Kelly N., Jarvis, Jacqueline M., Talipov, Marat R., and Yukl, Erik T.. Mon .
"Structural insights into the mechanism of oxidative activation of heme-free H-NOX from Vibrio cholerae". United States. https://doi.org/10.1042/bcj20200124. https://www.osti.gov/servlets/purl/1624989.
@article{osti_1624989,
title = {Structural insights into the mechanism of oxidative activation of heme-free H-NOX from Vibrio cholerae},
author = {Mukhopadhyay, Roma and Chacón, Kelly N. and Jarvis, Jacqueline M. and Talipov, Marat R. and Yukl, Erik T.},
abstractNote = {Bacterial heme nitric oxide/oxygen (H-NOX) domains are nitric oxide (NO) or oxygen sensors. This activity is mediated through binding of the ligand to a heme cofactor. However, H-NOX from Vibrio cholerae (Vc H-NOX) can be easily purified in a heme-free state that is capable of reversibly responding to oxidation, suggesting a heme-independent function as a redox sensor. This occurs by oxidation of Cys residues at a zinc-binding site conserved in a subset of H-NOX homologs. Remarkably, zinc is not lost from the protein upon oxidation, although its ligation environment is significantly altered. Using a combination of computational and experimental approaches, we have characterized localized structural changes that accompany the formation of specific disulfide bonds between Cys residues upon oxidation. Furthermore, the larger-scale structural changes accompanying oxidation appear to mimic those changes observed upon NO binding to the heme-bound form. Thus, Vc H-NOX and its homologs may act as both redox and NO sensors by completely separate mechanisms.},
doi = {10.1042/bcj20200124},
journal = {Biochemical Journal},
number = 6,
volume = 477,
place = {United States},
year = {2020},
month = {3}
}
Figures / Tables:

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journal, April 2005
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Transmissibility of cholera: In vivo-formed biofilms and their relationship to infectivity and persistence in the environment
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A structural basis for H-NOX signaling in Shewanella oneidensis by trapping a histidine kinase inhibitory conformation
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