DB code: D00084

CATH domain 3.40.1010.10 : Cobalt-precorrin-4 Transmethylase; domain 1 Catalytic domain
3.30.950.10 : Methyltransferase, Cobalt-precorrin-4 Transmethylase; Domain 2 Catalytic domain
E.C. 2.1.1.107
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam RefSeq
P21631 Uroporphyrinogen-III C-methyltransferase
Urogen III methylase
EC 2.1.1.107
SUMT
Uroporphyrinogen III methylase
UROM
PF00590 (TP_methylase)
[Graphical View]
Q5SKH6
Putative uncharacterized protein TTHA0667
PF00590 (TP_methylase)
[Graphical View]
YP_143933.1 (Protein)
NC_006461.1 (DNA/RNA sequence)
Q53WA2
S-adenosyl-L-methionine uroporphyrinogen methyltransferase
PF00590 (TP_methylase)
[Graphical View]
YP_145299.1 (Protein)
NC_006462.1 (DNA/RNA sequence)

KEGG enzyme name
uroporphyrinogen-III methyltransferase
uroporphyrinogen-III C-methyltransferase
uroporphyrinogen methyltransferase
adenosylmethionine-uroporphyrinogen III methyltransferase
S-adenosyl-L-methionine-dependent uroporphyrinogen III methylase
uroporphyrinogen-III methylase
SirA
CysG
CobA [ambiguous - see EC 2.5.1.17] SUMT
uroporphyrin-III C-methyltransferase (incorrect)
S-adenosyl-L-methionine:uroporphyrin-III C-methyltransferase(incorrect)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P21631 SUMT_PSEDE S-adenosyl-L-methionine + uroporphyrinogen III = S-adenosyl-L-homocysteine + precorrin-1. S-adenosyl-L-methionine + precorrin-1 = S- adenosyl-L-homocysteine + precorrin-2. Homodimer.
Q5SKH6 Q5SKH6_THET8 S-adenosyl-L-methionine + precorrin-1 = S- adenosyl-L-homocysteine + precorrin-2. S-adenosyl-L-methionine + uroporphyrinogen III = S-adenosyl-L-homocysteine + precorrin-1.
Q53WA2 Q53WA2_THET8 S-adenosyl-L-methionine + precorrin-1 = S- adenosyl-L-homocysteine + precorrin-2. S-adenosyl-L-methionine + uroporphyrinogen III = S-adenosyl-L-homocysteine + precorrin-1.

KEGG Pathways
Map code Pathways E.C.
MAP00860 Porphyrin and chlorophyll metabolism

Compound table
Substrates Products Intermediates
KEGG-id C00019 C01051 C15527 C00021 C15527 C02463
E.C.
Compound S-Adenosyl-L-methionine Uroporphyrinogen III Precorrin 1 S-Adenosyl-L-homocysteine Precorrin 1 Precorrin 2
Type amino acids,amine group,nucleoside,sulfonium ion aromatic ring (with nitrogen atoms),carboxyl group aromatic ring (with nitrogen atoms),carboxyl group amino acids,amine group,nucleoside,sulfide group aromatic ring (with nitrogen atoms),carboxyl group amine group,aromatic ring (with nitrogen atoms),carboxyl group
ChEBI 67040
15437
52469
16680
57856
52469
PubChem 34755
1179
11954200
25246222
439155
11954200
5280516
1s4dA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1s4dB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1s4dD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1s4dE01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1s4dF01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1s4dG01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1s4dH01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1s4dI01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1s4dJ01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1s4dK01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1s4dL01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1s4dM01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1v9aA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1v9aB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1va0A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1va0B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1ve2A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1ve2B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1s4dA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:SAH Unbound Unbound
1s4dB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:SAH Unbound Unbound
1s4dD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:SAH Unbound Unbound
1s4dE02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:SAH Unbound Unbound
1s4dF02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:SAH Unbound Unbound
1s4dG02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:SAH Unbound Unbound
1s4dH02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:SAH Unbound Unbound
1s4dI02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:SAH Unbound Unbound
1s4dJ02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:SAH Unbound Unbound
1s4dK02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:SAH Unbound Unbound
1s4dL02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:SAH Unbound Unbound
1s4dM02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:SAH Unbound Unbound
1v9aA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:SAH Unbound Unbound
1v9aB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:SAH Unbound Unbound
1va0A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1va0B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1ve2A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1ve2B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [9], [10], [11]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1s4dA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 47;LYS 69 invisible 72-73
1s4dB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 47;LYS 69
1s4dD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 47; invisible 69-73
1s4dE01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 47;LYS 69
1s4dF01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 47;LYS 69 invisible 70-72, side chain of K69
1s4dG01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 47;LYS 69
1s4dH01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 47;LYS 69 invisible side chain of K69
1s4dI01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 47;LYS 69 invisible 73
1s4dJ01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 47;LYS 69 invisible 70-72, side chain of K69
1s4dK01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 47;LYS 69 invisible 73
1s4dL01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 47;LYS 69 invisible 70, 76, side chain of K69
1s4dM01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 47;LYS 69 invisible 73
1v9aA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 34;LYS 54 invisible 55-60, side chain of K54
1v9aB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 34;LYS 54 invisible 55-63, side chain of K54
1va0A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 34;LYS 54 invisible 57-60
1va0B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 34; invisible 53-62
1ve2A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 35; invisible 54-60
1ve2B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 35; invisible 54-63
1s4dA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 159-165
1s4dB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 163
1s4dD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 163-166
1s4dE02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 163-164
1s4dF02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 159-163
1s4dG02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 163-164
1s4dH02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 160-166
1s4dI02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 162-163
1s4dJ02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 160-166
1s4dK02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1s4dL02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 159-163
1s4dM02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 160-166
1v9aA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1v9aB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1va0A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1va0B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ve2A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 161-166
1ve2B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
p.588-589
[9]
p.1068-1069
[10]
Fig.1, p.429-430

References
[1]
Resource
Comments CHARACTERIZATION.
Medline ID
PubMed ID 2546914
Journal J Bacteriol
Year 1989
Volume 171
Pages 4222-31
Authors Blanche F, Debussche L, Thibaut D, Crouzet J, Cameron B
Title Purification and characterization of S-adenosyl-L-methionine: uroporphyrinogen III methyltransferase from Pseudomonas denitrificans.
Related PDB
Related UniProtKB P21631
[2]
Resource
Comments
Medline ID
PubMed ID 1508200
Journal Mol Cell Biol
Year 1992
Volume 12
Pages 4026-37
Authors Mattheakis LC, Shen WH, Collier RJ
Title DPH5, a methyltransferase gene required for diphthamide biosynthesis in Saccharomyces cerevisiae.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8501034
Journal J Bacteriol
Year 1993
Volume 175
Pages 3303-16
Authors Roth JR, Lawrence JG, Rubenfield M, Kieffer-Higgins S, Church GM
Title Characterization of the cobalamin (vitamin B12) biosynthetic genes of Salmonella typhimurium.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9461500
Journal Biochem J
Year 1998
Volume 330
Pages 121-9
Authors Woodcock SC, Raux E, Levillayer F, Thermes C, Rambach A, Warren MJ
Title Effect of mutations in the transmethylase and dehydrogenase/chelatase domains of sirohaem synthase (CysG) on sirohaem and cobalamin biosynthesis.
Related PDB
Related UniProtKB
[5]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9665173
Journal Nat Struct Biol
Year 1998
Volume 5
Pages 585-92
Authors Schubert HL, Wilson KS, Raux E, Woodcock SC, Warren MJ
Title The X-ray structure of a cobalamin biosynthetic enzyme, cobalt-precorrin-4 methyltransferase.
Related PDB 1cbf 2cbf
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10400331
Journal Bioorg Med Chem
Year 1999
Volume 7
Pages 789-94
Authors Santander PJ, Stolowich NJ, Scott AI
Title Chemoenzymatic synthesis of an unnatural tetramethyl cobalt corphinoid.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 12195810
Journal Nat Prod Rep
Year 2002
Volume 19
Pages 390-412
Authors Warren MJ, Raux E, Schubert HL, Escalante-Semerena JC
Title The biosynthesis of adenosylcobalamin (vitamin B12).
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 12662021
Journal J Org Chem
Year 2003
Volume 68
Pages 2529-39
Authors Scott AI
Title Discovering nature's diverse pathways to vitamin B12: a 35-year odyssey.
Related PDB
Related UniProtKB
[9]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 14595395
Journal Nat Struct Biol
Year 2003
Volume 10
Pages 1064-73
Authors Stroupe ME, Leech HK, Daniels DS, Warren MJ, Getzoff ED
Title CysG structure reveals tetrapyrrole-binding features and novel regulation of siroheme biosynthesis.
Related PDB 1pjq 1pjs 1pjt
Related UniProtKB
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF APOPROTEIN IN COMPLEX WITH S-ADENOSYL-L-METHIONINE, SUBUNIT, KINETIC PARAMETERS, AND MUTAGENESIS OF ASP-47; LEU-49; PHE-106; THR-130; TYR-183 AND MET-184.
Medline ID
PubMed ID 15522295
Journal J Mol Biol
Year 2004
Volume 344
Pages 419-33
Authors Vevodova J, Graham RM, Raux E, Schubert HL, Roper DI, Brindley AA, Ian Scott A, Roessner CA, Stamford NP, Elizabeth Stroupe M, Getzoff ED, Warren MJ, Wilson KS
Title Structure/function studies on a S-adenosyl-L-methionine-dependent uroporphyrinogen III C methyltransferase (SUMT), a key regulatory enzyme of tetrapyrrole biosynthesis.
Related PDB 1s4d
Related UniProtKB P21631
[11]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 15983414
Journal Acta Crystallogr D Biol Crystallogr
Year 2005
Volume 61
Pages 913-9
Authors Rehse PH, Kitao T, Tahirov TH
Title Structure of a closed-form uroporphyrinogen-III C-methyltransferase from Thermus thermophilus.
Related PDB 1v9a 1va0
Related UniProtKB
[12]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 17229157
Journal FEBS J
Year 2007
Volume 274
Pages 563-73
Authors Wada K, Harada J, Yaeda Y, Tamiaki H, Oh-Oka H, Fukuyama K
Title Crystal structures of CbiL, a methyltransferase involved in anaerobic vitamin B biosynthesis, and CbiL in complex with S-adenosylhomocysteine - implications for the reaction mechanism.
Related PDB 2e0k 2e0n
Related UniProtKB

Comments
According to the literature [10], this enzyme catalyzes the following reactions:
(A) Transfer of methyl group from the sulfur atom of SAM to the C2 (sp2 carbon) of uroporphyrinogen III:
(B) Isomerization; Shift of double-bond position (from N=C-C to N-C=C):
(C) Isomerization; Shift of double-bond position (from C=C-C to C-C=C), forming precorrin-1:
(D) Transfer of methyl group from the sulfur atom of SAM to the C7 (sp2 carbon) of precorrin-1:
(E) Isomerization; Shift of double-bond position (from N=C-C to N-C=C):
(F) Isomerization; Shift of double-bond position (from C=C-C to C-C=C), producing precorrin-2:
###
During the following reactions, Asp47 (PDB;1s4d) acts as a general base to deprotonate the C5 or C10 methylene.
(C) Isomerization; Shift of double-bond position (from C=C-C to C-C=C), forming precorrin-1:
(F) Isomerization; Shift of double-bond position (from C=C-C to C-C=C), producing precorrin-2:

Created Updated
2007-02-19 2009-04-03