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Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site

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 bifun...

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Autores principales: Pennington, Joseph M., Kemp, Michael, McGarry, Lauren, Chen, Yu, Stroupe, M. Elizabeth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018833/
https://www.ncbi.nlm.nih.gov/pubmed/32054833
http://dx.doi.org/10.1038/s41467-020-14722-1
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author Pennington, Joseph M.
Kemp, Michael
McGarry, Lauren
Chen, Yu
Stroupe, M. Elizabeth
author_facet Pennington, Joseph M.
Kemp, Michael
McGarry, Lauren
Chen, Yu
Stroupe, M. Elizabeth
author_sort Pennington, Joseph M.
collection PubMed
description 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.
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spelling pubmed-70188332020-02-21 Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site Pennington, Joseph M. Kemp, Michael McGarry, Lauren Chen, Yu Stroupe, M. Elizabeth Nat Commun Article 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. Nature Publishing Group UK 2020-02-13 /pmc/articles/PMC7018833/ /pubmed/32054833 http://dx.doi.org/10.1038/s41467-020-14722-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
title Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site
title_full Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site
title_fullStr Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site
title_full_unstemmed Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site
title_short Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site
title_sort siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018833/
https://www.ncbi.nlm.nih.gov/pubmed/32054833
http://dx.doi.org/10.1038/s41467-020-14722-1
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