6P5Z

Cobalt-sirohydrochlorin-bound S. typhimurium siroheme synthase

Summary for 6P5Z

• Entry DOI: 10.2210/pdb6p5z/pdb
• Related: 6P5X
• Descriptor: Siroheme synthase, S-ADENOSYL-L-HOMOCYSTEINE, cobalt-sirohydrochlorin, ... (5 entities in total)
• Functional Keywords: tetrapyrrole biosynthesis, cysg, biosynthetic protein
• Biological source: Salmonella typhimurium
• Total number of polymer chains: 2
• Total formula weight: 103060.23

Authors

Pennington, J.M.,Stroupe, M.E. (deposition date: 2019-05-31, release date: 2021-06-16, Last modification date: 2023-10-11)

Primary citation

Pennington, J.M.,Kemp, M.,McGarry, L.,Chen, Y.,Stroupe, M.E.
Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site.
Nat Commun, 11:864-864, 2020

PubMed 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.

PubMed: 32054833
DOI: 10.1038/s41467-020-14722-1

Experimental method

X-RAY DIFFRACTION (2.26 Å)