6PR2

R261A/S128A S. typhimurium siroheme synthase

Summary for 6PR2

• Entry DOI: 10.2210/pdb6pr2/pdb
• Related: 1PJS
• Descriptor: Siroheme synthase, CHLORIDE ION, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (5 entities in total)
• Functional Keywords: precorrin-2, tetrapyrrole biosynthesis, cysg, transferase
• Biological source: Salmonella typhimurium
• Total number of polymer chains: 2
• Total formula weight: 101279.18

Authors

Pennington, J.M.,Stroupe, M.E. (deposition date: 2019-07-10, release date: 2020-02-26, 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 (2.16 Å)