PDBsum entry 6p7c

Transferase

PDB id: 6p7c

Contents

Protein chains

451 a.a.

Ligands

SAH ×2

Metals

_CL

Waters ×48

PDB id:

6p7c

Name:

Transferase

Title:

D104a/s128a s. Typhimurium siroheme synthase

Structure:

Siroheme synthase. Chain: a, b. Engineered: yes. Mutation: yes

Source:

Salmonella typhimurium. Organism_taxid: 90371. Gene: cysg, coba, aap89_23165, abo94_22995, af480_23265, af488_22710, af489_21700, aic76_23675, axr84_23260, axu58_22185, c2253_19735, cd48_22680, ce87_23070, cet98_25025, cvr97_13625, d7f20_23535, d7h43_21790, dj388_17225, dm376_19045, e2f01_22980, fcj89_03505, fg594_22565, fg605_22440, fg608_22845, fg609_22120, fg610_23420, fg612_22925, fg614_17700, fg736_21980, fjv50_24115, fjv51_21965, fjv53_21305, fjv54_21440, fjv55_23340, fjv56_23845,

Resolution:

2.76Å R-factor: 0.193 R-free: 0.285

Authors:

J.M.Pennington,M.E.Stroupe

Key ref:

J.M.Pennington et al. (2020). Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site. Nat Commun, 11, 864. PubMed id: 32054833 DOI: 10.1038/s41467-020-14722-1

Date:

05-Jun-19 Release date: 26-Feb-20

Protein chains

P25924  (CYSG_SALTY) -  Siroheme synthase from Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)

Seq: 457 a.a.

Struc: 451 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.1.3.1.76 - precorrin-2 dehydrogenase.
• Pathway: Corrin and Siroheme Biosynthesis (part 2)
• Reaction: precorrin-2 + NAD⁺ = sirohydrochlorin + NADH + 2 H⁺
• Enzyme class 2: E.C.2.1.1.107 - uroporphyrinogen-III C-methyltransferase.

Pathway:

• Reaction: uroporphyrinogen III + 2 S-adenosyl-L-methionine = precorrin-2 + 2 S-adenosyl-L-homocysteine + H⁺

uroporphyrinogen III + 2 × S-adenosyl-L-methionine = precorrin-2 + 2 × S-adenosyl-L-homocysteine + 2 × H(+) (Bound ligand (Het Group name = SAH) corresponds exactly)

• Enzyme class 3: E.C.4.99.1.4 - sirohydrochlorin ferrochelatase.

Pathway:

• Reaction: siroheme + 2 H⁺ = sirohydrochlorin + Fe²⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/s41467-020-14722-1

Nat Commun 11:864 (2020)

PubMed id: 32054833

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

J.M.Pennington, M.Kemp, L.McGarry, Y.Chen, M.E.Stroupe.

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.