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Structure and function of CysG, the multifunctional methyltransferase/dehydrogenase/ferrochelatase for siroheme synthesis

Source organism: Salmonella enterica subsp. enterica serovar Typhimurium
Biochemical function: NAD binding
Biological process: methylation
Cellular component: not assigned

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EC 2.1.1.107: Uroporphyrinogen-III C-methyltransferase

Reaction catalysed:
(1a) S-adenosyl-L-methionine + uroporphyrinogen III = S-adenosyl-L-homocysteine + precorrin-1
Systematic name:
S-adenosyl-L-methionine:uroporphyrinogen-III C-methyltransferase
Alternative Name(s):
  • Adenosylmethionine-uroporphyrinogen III methyltransferase
  • CobA
  • CysG
  • S-adenosyl-L-methionine-dependent uroporphyrinogen III methylase
  • S-adenosyl-L-methionine:uroporphyrin-III C-methyltransferase
  • SUMT
  • SirA
  • Urogen III methylase
  • Uroporphyrin-III C-methyltransferase
  • Uroporphyrinogen III methylase
  • Uroporphyrinogen methyltransferase
  • Uroporphyrinogen-III methylase
  • Uroporphyrinogen-III methyltransferase

EC 4.99.1.4: Sirohydrochlorin ferrochelatase

Reaction catalysed:
Siroheme + 2 H(+) = sirohydrochlorin + Fe(2+)
Systematic name:
Siroheme ferro-lyase (sirohydrochlorin-forming)
Alternative Name(s):
  • CysG
  • Met8P
  • SirB
  • Sirohydrochlorin ferro-lyase

EC 1.3.1.76: Precorrin-2 dehydrogenase

Reaction catalysed:
Precorrin-2 + NAD(+) = sirohydrochlorin + NADH
Systematic name:
Precorrin-2:NAD(+) oxidoreductase
Alternative Name(s):
  • CysG
  • Met8p
  • Precorrin-2 oxidase
  • SirC

GO terms

Sequence families

Pfam Protein families (Pfam)
PF00590
Domain description: Tetrapyrrole (Corrin/Porphyrin) Methylases
Occurring in:
  1. Siroheme synthase
The deposited structure of PDB entry 1pjq contains 2 copies of Pfam domain PF00590 (Tetrapyrrole (Corrin/Porphyrin) Methylases) in Siroheme synthase. Showing 1 copy in chain B.

PF10414
Domain description: Sirohaem synthase dimerisation region
Occurring in:
  1. Siroheme synthase
The deposited structure of PDB entry 1pjq contains 2 copies of Pfam domain PF10414 (Sirohaem synthase dimerisation region) in Siroheme synthase. Showing 1 copy in chain B.

PF14824
Domain description: Sirohaem biosynthesis protein central
Occurring in:
  1. Siroheme synthase
The deposited structure of PDB entry 1pjq contains 2 copies of Pfam domain PF14824 (Sirohaem biosynthesis protein central) in Siroheme synthase. Showing 1 copy in chain B.

PF13241
Domain description: Putative NAD(P)-binding
Occurring in:
  1. Siroheme synthase
The deposited structure of PDB entry 1pjq contains 2 copies of Pfam domain PF13241 (Putative NAD(P)-binding) in Siroheme synthase. Showing 1 copy in chain B.

InterPro InterPro annotations
IPR006366
Domain description: Uroporphyrin-III C-methyltransferase
Occurring in:
  1. Siroheme synthase
IPR003043
Domain description: Uroporphiryn-III C-methyltransferase, conserved site
Occurring in:
  1. Siroheme synthase
IPR014776
Domain description: Tetrapyrrole methylase, subdomain 2
Occurring in:
  1. Siroheme synthase
IPR000878
Domain description: Tetrapyrrole methylase
Occurring in:
  1. Siroheme synthase
IPR035996
Domain description: Tetrapyrrole methylase superfamily
Occurring in:
  1. Siroheme synthase
IPR014777
Domain description: Tetrapyrrole methylase, subdomain 1
Occurring in:
  1. Siroheme synthase
IPR019478
Domain description: Sirohaem synthase, dimerisation domain
Occurring in:
  1. Siroheme synthase
IPR037115
Domain description: Sirohaem synthase, dimerisation domain superfamily
Occurring in:
  1. Siroheme synthase
IPR028281
Domain description: Siroheme synthase, central domain
Occurring in:
  1. Siroheme synthase
IPR006367
Domain description: Sirohaem synthase, N-terminal
Occurring in:
  1. Siroheme synthase
IPR036291
Domain description: NAD(P)-binding domain superfamily
Occurring in:
  1. Siroheme synthase
IPR012409
Domain description: Sirohaem synthase
Occurring in:
  1. Siroheme synthase

Structure domains

CATH CATH domains
3.30.950.10
Class: Alpha Beta
Architecture: 2-Layer Sandwich
Topology: Methyltransferase, Cobalt-precorrin-4 Transmethylase; Domain 2
Homology: Methyltransferase, Cobalt-precorrin-4 Transmethylase; Domain 2
Occurring in:
  1. Siroheme synthase
The deposited structure of PDB entry 1pjq contains 2 copies of CATH domain 3.30.950.10 (Methyltransferase, Cobalt-precorrin-4 Transmethylase; Domain 2) in Siroheme synthase. Showing 1 copy in chain B.
3.40.1010.10
Class: Alpha Beta
Architecture: 3-Layer(aba) Sandwich
Topology: Cobalt-precorrin-4 Transmethylase; domain 1
Homology: Cobalt-precorrin-4 Transmethylase; Domain 1
Occurring in:
  1. Siroheme synthase
The deposited structure of PDB entry 1pjq contains 2 copies of CATH domain 3.40.1010.10 (Cobalt-precorrin-4 Transmethylase; domain 1) in Siroheme synthase. Showing 1 copy in chain B.
1.10.8.210
Class: Mainly Alpha
Architecture: Orthogonal Bundle
Topology: Helicase, Ruva Protein; domain 3
Homology: Sirohaem synthase, dimerisation domain
Occurring in:
  1. Siroheme synthase
The deposited structure of PDB entry 1pjq contains 2 copies of CATH domain 1.10.8.210 (Helicase, Ruva Protein; domain 3) in Siroheme synthase. Showing 1 copy in chain B.
3.30.160.110
Class: Alpha Beta
Architecture: 2-Layer Sandwich
Topology: Double Stranded RNA Binding Domain
Homology: Siroheme synthase; domain 2
Occurring in:
  1. Siroheme synthase
The deposited structure of PDB entry 1pjq contains 2 copies of CATH domain 3.30.160.110 (Double Stranded RNA Binding Domain) in Siroheme synthase. Showing 1 copy in chain B.
3.40.50.720
Class: Alpha Beta
Architecture: 3-Layer(aba) Sandwich
Topology: Rossmann fold
Homology: NAD(P)-binding Rossmann-like Domain
Occurring in:
  1. Siroheme synthase
The deposited structure of PDB entry 1pjq contains 2 copies of CATH domain 3.40.50.720 (Rossmann fold) in Siroheme synthase. Showing 1 copy in chain B.
SCOP SCOP annotations
53791
Class: Alpha and beta proteins (a/b)
Fold: Tetrapyrrole methylase
Superfamily: Tetrapyrrole methylase
Occurring in:
  1. Siroheme synthase
The deposited structure of PDB entry 1pjq contains 2 copies of SCOP domain 53791 (Tetrapyrrole methylase) in Siroheme synthase. Showing 1 copy in chain B.
75616
Class: Multi-domain proteins (alpha and beta)
Fold: Siroheme synthase middle domains-like
Superfamily: Siroheme synthase middle domains-like
Occurring in:
  1. Siroheme synthase
The deposited structure of PDB entry 1pjq contains 2 copies of SCOP domain 75616 (Siroheme synthase middle domains-like) in Siroheme synthase. Showing 1 copy in chain B.
75110
Class: Alpha and beta proteins (a/b)
Fold: NAD(P)-binding Rossmann-fold domains
Superfamily: NAD(P)-binding Rossmann-fold domains
Occurring in:
  1. Siroheme synthase
The deposited structure of PDB entry 1pjq contains 2 copies of SCOP domain 75110 (Siroheme synthase N-terminal domain-like) in Siroheme synthase. Showing 1 copy in chain B.

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