Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site
Abstract
Siroheme is the central cofactor in a conserved class of sulfite and nitrite reductases that catalyze the six-electron reduction of sulfite to sulfide and nitrite to ammonia. In Salmonella enterica serovar Typhimurium, siroheme is produced by a trifunctional enzyme, siroheme synthase (CysG). A bifunctional active site that is distinct from its methyltransferase activity catalyzes the final two steps, NAD+-dependent dehydrogenation and iron chelation. How this active site performs such different chemistries is unknown. Here, we report the structures of CysG bound to precorrin-2, the initial substrate; sirohydrochlorin, the dehydrogenation product/chelation substrate; and a cobalt-sirohydrochlorin product. We identified binding poses for all three tetrapyrroles and tested the roles of specific amino acids in both activities to give insights into how a bifunctional active site catalyzes two different chemistries and acts as an iron-specific chelatase in the final step of siroheme synthesis.
- Authors:
-
[1];
[2];
[2];
[1]
- Florida State Univ., Tallahassee, FL (United States)
- Univ. of South Florida, Tampa, FL (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- National Science Foundation (NSF)
- OSTI Identifier:
- 1601850
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Communications
- Additional Journal Information:
- Journal Volume: 11; Journal Issue: 1; Journal ID: ISSN 2041-1723
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Citation Formats
Pennington, Joseph M., Kemp, Michael, McGarry, Lauren, Chen, Yu, and Stroupe, M. Elizabeth. Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site. United States: N. p., 2020.
Web. doi:10.1038/s41467-020-14722-1.
Pennington, Joseph M., Kemp, Michael, McGarry, Lauren, Chen, Yu, & Stroupe, M. Elizabeth. Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site. United States. https://doi.org/10.1038/s41467-020-14722-1
Pennington, Joseph M., Kemp, Michael, McGarry, Lauren, Chen, Yu, and Stroupe, M. Elizabeth. Thu .
"Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site". United States. https://doi.org/10.1038/s41467-020-14722-1. https://www.osti.gov/servlets/purl/1601850.
@article{osti_1601850,
title = {Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site},
author = {Pennington, Joseph M. and Kemp, Michael and McGarry, Lauren and Chen, Yu and Stroupe, M. Elizabeth},
abstractNote = {Siroheme is the central cofactor in a conserved class of sulfite and nitrite reductases that catalyze the six-electron reduction of sulfite to sulfide and nitrite to ammonia. In Salmonella enterica serovar Typhimurium, siroheme is produced by a trifunctional enzyme, siroheme synthase (CysG). A bifunctional active site that is distinct from its methyltransferase activity catalyzes the final two steps, NAD+-dependent dehydrogenation and iron chelation. How this active site performs such different chemistries is unknown. Here, we report the structures of CysG bound to precorrin-2, the initial substrate; sirohydrochlorin, the dehydrogenation product/chelation substrate; and a cobalt-sirohydrochlorin product. We identified binding poses for all three tetrapyrroles and tested the roles of specific amino acids in both activities to give insights into how a bifunctional active site catalyzes two different chemistries and acts as an iron-specific chelatase in the final step of siroheme synthesis.},
doi = {10.1038/s41467-020-14722-1},
journal = {Nature Communications},
number = 1,
volume = 11,
place = {United States},
year = {Thu Feb 13 00:00:00 EST 2020},
month = {Thu Feb 13 00:00:00 EST 2020}
}
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