Structural highlights
Function
[A0A0F7JCI1_SALER] Multifunctional enzyme that catalyzes the SAM-dependent methylations of uroporphyrinogen III at position C-2 and C-7 to form precorrin-2 via precorrin-1. Then it catalyzes the NAD-dependent ring dehydrogenation of precorrin-2 to yield sirohydrochlorin. Finally, it catalyzes the ferrochelation of sirohydrochlorin to yield siroheme.[HAMAP-Rule:MF_01646][SAAS:SAAS00971394]
Publication Abstract from PubMed
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.
Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site.,Pennington JM, Kemp M, McGarry L, Chen Y, Stroupe ME Nat Commun. 2020 Feb 13;11(1):864. doi: 10.1038/s41467-020-14722-1. PMID:32054833[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pennington JM, Kemp M, McGarry L, Chen Y, Stroupe ME. Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site. Nat Commun. 2020 Feb 13;11(1):864. doi: 10.1038/s41467-020-14722-1. PMID:32054833 doi:http://dx.doi.org/10.1038/s41467-020-14722-1
