%APennington, Joseph%AKemp, Michael%AMcGarry, Lauren%AChen, Yu%AStroupe, M.%BJournal Name: Nature Communications; Journal Volume: 11; Journal Issue: 1; Related Information: CHORUS Timestamp: 2021-12-02 01:39:44 %D2020%INature Publishing Group %JJournal Name: Nature Communications; Journal Volume: 11; Journal Issue: 1; Related Information: CHORUS Timestamp: 2021-12-02 01:39:44 %K %MOSTI ID: 10153441 %PMedium: X %TSiroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site %XAbstract

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. InSalmonella entericaserovar 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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