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

doi:10.1038/s41467-020-14722-1

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

Journal Article · 13 February 2020 · Nature Communications

DOI: https://doi.org/10.1038/s41467-020-14722-1 · OSTI ID:1601850

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^[2]; McGarry, Lauren ^[1];

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Florida State Univ., Tallahassee, FL (United States)
Univ. of South Florida, Tampa, FL (United States)

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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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Science Foundation (NSF)

OSTI ID:: 1601850

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 11; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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