EzCatDB: D00084
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DB codeD00084
CATH domainDomain 13.40.1010.10 : Cobalt-precorrin-4 Transmethylase; domain 1Catalytic domain
Domain 23.30.950.10 : Methyltransferase, Cobalt-precorrin-4 Transmethylase; Domain 2Catalytic domain
E.C.2.1.1.107


Enzyme Name
UniProtKBKEGG

P21631Q5SKH6Q53WA2
Protein nameUroporphyrinogen-III C-methyltransferase

uroporphyrinogen-III C-methyltransferase
uroporphyrinogen methyltransferase
uroporphyrinogen-III 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)
SynonymsUrogen III methylase
EC 2.1.1.107
SUMT
Uroporphyrinogen III methylase
UROM
Putative uncharacterized protein TTHA0667
S-adenosyl-L-methionine uroporphyrinogen methyltransferase
RefSeq
YP_143933.1 (Protein)
NC_006461.1 (DNA/RNA sequence)
YP_145299.1 (Protein)
NC_006462.1 (DNA/RNA sequence)
PfamPF00590 (TP_methylase)
[Graphical view]
PF00590 (TP_methylase)
[Graphical view]
PF00590 (TP_methylase)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00860Porphyrin and chlorophyll metabolism

UniProtKB:Accession NumberP21631Q5SKH6Q53WA2
Entry nameSUMT_PSEDEQ5SKH6_THET8Q53WA2_THET8
ActivityS-adenosyl-L-methionine + uroporphyrinogen III = S-adenosyl-L-homocysteine + precorrin-1.,S-adenosyl-L-methionine + precorrin-1 = S- adenosyl-L-homocysteine + precorrin-2.S-adenosyl-L-methionine + precorrin-1 = S- adenosyl-L-homocysteine + precorrin-2.,S-adenosyl-L-methionine + uroporphyrinogen III = S-adenosyl-L-homocysteine + precorrin-1.S-adenosyl-L-methionine + precorrin-1 = S- adenosyl-L-homocysteine + precorrin-2.,S-adenosyl-L-methionine + uroporphyrinogen III = S-adenosyl-L-homocysteine + precorrin-1.
SubunitHomodimer.

Subcellular location


Cofactor



Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00019C01051C15527C00021C15527C02463
CompoundS-Adenosyl-L-methionineUroporphyrinogen IIIPrecorrin 1S-Adenosyl-L-homocysteinePrecorrin 1Precorrin 2
Typeamino acids,amine group,nucleoside,sulfonium ionaromatic ring (with nitrogen atoms),carboxyl grouparomatic ring (with nitrogen atoms),carboxyl groupamino acids,amine group,nucleoside,sulfide grouparomatic ring (with nitrogen atoms),carboxyl groupamine group,aromatic ring (with nitrogen atoms),carboxyl group
ChEBI67040
15437
52469
16680
57856
52469

PubChem34755
1179
11954200
439155
25246222
11954200
5280516
              
1s4dA01UnboundUnboundUnboundUnboundUnboundUnbound
1s4dB01UnboundUnboundUnboundUnboundUnboundUnbound
1s4dD01UnboundUnboundUnboundUnboundUnboundUnbound
1s4dE01UnboundUnboundUnboundUnboundUnboundUnbound
1s4dF01UnboundUnboundUnboundUnboundUnboundUnbound
1s4dG01UnboundUnboundUnboundUnboundUnboundUnbound
1s4dH01UnboundUnboundUnboundUnboundUnboundUnbound
1s4dI01UnboundUnboundUnboundUnboundUnboundUnbound
1s4dJ01UnboundUnboundUnboundUnboundUnboundUnbound
1s4dK01UnboundUnboundUnboundUnboundUnboundUnbound
1s4dL01UnboundUnboundUnboundUnboundUnboundUnbound
1s4dM01UnboundUnboundUnboundUnboundUnboundUnbound
1v9aA01UnboundUnboundUnboundUnboundUnboundUnbound
1v9aB01UnboundUnboundUnboundUnboundUnboundUnbound
1va0A01UnboundUnboundUnboundUnboundUnboundUnbound
1va0B01UnboundUnboundUnboundUnboundUnboundUnbound
1ve2A01UnboundUnboundUnboundUnboundUnboundUnbound
1ve2B01UnboundUnboundUnboundUnboundUnboundUnbound
1s4dA02UnboundUnboundUnboundBound:SAHUnboundUnbound
1s4dB02UnboundUnboundUnboundBound:SAHUnboundUnbound
1s4dD02UnboundUnboundUnboundBound:SAHUnboundUnbound
1s4dE02UnboundUnboundUnboundBound:SAHUnboundUnbound
1s4dF02UnboundUnboundUnboundBound:SAHUnboundUnbound
1s4dG02UnboundUnboundUnboundBound:SAHUnboundUnbound
1s4dH02UnboundUnboundUnboundBound:SAHUnboundUnbound
1s4dI02UnboundUnboundUnboundBound:SAHUnboundUnbound
1s4dJ02UnboundUnboundUnboundBound:SAHUnboundUnbound
1s4dK02UnboundUnboundUnboundBound:SAHUnboundUnbound
1s4dL02UnboundUnboundUnboundBound:SAHUnboundUnbound
1s4dM02UnboundUnboundUnboundBound:SAHUnboundUnbound
1v9aA02UnboundUnboundUnboundBound:SAHUnboundUnbound
1v9aB02UnboundUnboundUnboundBound:SAHUnboundUnbound
1va0A02UnboundUnboundUnboundUnboundUnboundUnbound
1va0B02UnboundUnboundUnboundUnboundUnboundUnbound
1ve2A02UnboundUnboundUnboundUnboundUnboundUnbound
1ve2B02UnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
literature [9], [10], [11]
pdbCatalytic residuescomment
          
1s4dA01ASP 47;LYS 69
invisible 72-73
1s4dB01ASP 47;LYS 69
 
1s4dD01ASP 47;      
invisible 69-73
1s4dE01ASP 47;LYS 69
 
1s4dF01ASP 47;LYS 69
invisible 70-72, side chain of K69
1s4dG01ASP 47;LYS 69
 
1s4dH01ASP 47;LYS 69
invisible side chain of K69
1s4dI01ASP 47;LYS 69
invisible 73
1s4dJ01ASP 47;LYS 69
invisible 70-72, side chain of K69
1s4dK01ASP 47;LYS 69
invisible 73
1s4dL01ASP 47;LYS 69
invisible 70, 76, side chain of K69
1s4dM01ASP 47;LYS 69
invisible 73
1v9aA01ASP 34;LYS 54
invisible 55-60, side chain of K54
1v9aB01ASP 34;LYS 54
invisible 55-63, side chain of K54
1va0A01ASP 34;LYS 54
invisible 57-60
1va0B01ASP 34;      
invisible 53-62
1ve2A01ASP 35;      
invisible 54-60
1ve2B01ASP 35;      
invisible 54-63
1s4dA02 
invisible 159-165
1s4dB02 
invisible 163
1s4dD02 
invisible 163-166
1s4dE02 
invisible 163-164
1s4dF02 
invisible 159-163
1s4dG02 
invisible 163-164
1s4dH02 
invisible 160-166
1s4dI02 
invisible 162-163
1s4dJ02 
invisible 160-166
1s4dK02 
 
1s4dL02 
invisible 159-163
1s4dM02 
invisible 160-166
1v9aA02 
 
1v9aB02 
 
1va0A02 
 
1va0B02 
 
1ve2A02 
invisible 161-166
1ve2B02 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]p.588-589
[9]p.1068-1069
[10]Fig.1, p.429-430

references
[1]
CommentsCHARACTERIZATION.
PubMed ID2546914
JournalJ Bacteriol
Year1989
Volume171
Pages4222-31
AuthorsBlanche F, Debussche L, Thibaut D, Crouzet J, Cameron B
TitlePurification and characterization of S-adenosyl-L-methionine: uroporphyrinogen III methyltransferase from Pseudomonas denitrificans.
Related UniProtKBP21631
[2]
PubMed ID1508200
JournalMol Cell Biol
Year1992
Volume12
Pages4026-37
AuthorsMattheakis LC, Shen WH, Collier RJ
TitleDPH5, a methyltransferase gene required for diphthamide biosynthesis in Saccharomyces cerevisiae.
[3]
PubMed ID8501034
JournalJ Bacteriol
Year1993
Volume175
Pages3303-16
AuthorsRoth JR, Lawrence JG, Rubenfield M, Kieffer-Higgins S, Church GM
TitleCharacterization of the cobalamin (vitamin B12) biosynthetic genes of Salmonella typhimurium.
[4]
PubMed ID9461500
JournalBiochem J
Year1998
Volume330
Pages121-9
AuthorsWoodcock SC, Raux E, Levillayer F, Thermes C, Rambach A, Warren MJ
TitleEffect of mutations in the transmethylase and dehydrogenase/chelatase domains of sirohaem synthase (CysG) on sirohaem and cobalamin biosynthesis.
[5]
CommentsX-ray crystallography
PubMed ID9665173
JournalNat Struct Biol
Year1998
Volume5
Pages585-92
AuthorsSchubert HL, Wilson KS, Raux E, Woodcock SC, Warren MJ
TitleThe X-ray structure of a cobalamin biosynthetic enzyme, cobalt-precorrin-4 methyltransferase.
Related PDB1cbf,2cbf
[6]
PubMed ID10400331
JournalBioorg Med Chem
Year1999
Volume7
Pages789-94
AuthorsSantander PJ, Stolowich NJ, Scott AI
TitleChemoenzymatic synthesis of an unnatural tetramethyl cobalt corphinoid.
[7]
PubMed ID12195810
JournalNat Prod Rep
Year2002
Volume19
Pages390-412
AuthorsWarren MJ, Raux E, Schubert HL, Escalante-Semerena JC
TitleThe biosynthesis of adenosylcobalamin (vitamin B12).
[8]
PubMed ID12662021
JournalJ Org Chem
Year2003
Volume68
Pages2529-39
AuthorsScott AI
TitleDiscovering nature's diverse pathways to vitamin B12: a 35-year odyssey.
[9]
CommentsX-ray crystallography
PubMed ID14595395
JournalNat Struct Biol
Year2003
Volume10
Pages1064-73
AuthorsStroupe ME, Leech HK, Daniels DS, Warren MJ, Getzoff ED
TitleCysG structure reveals tetrapyrrole-binding features and novel regulation of siroheme biosynthesis.
Related PDB1pjq,1pjs,1pjt
[10]
CommentsX-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.
PubMed ID15522295
JournalJ Mol Biol
Year2004
Volume344
Pages419-33
AuthorsVevodova 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
TitleStructure/function studies on a S-adenosyl-L-methionine-dependent uroporphyrinogen III C methyltransferase (SUMT), a key regulatory enzyme of tetrapyrrole biosynthesis.
Related PDB1s4d
Related UniProtKBP21631
[11]
CommentsX-ray crystallography
PubMed ID15983414
JournalActa Crystallogr D Biol Crystallogr
Year2005
Volume61
Pages913-9
AuthorsRehse PH, Kitao T, Tahirov TH
TitleStructure of a closed-form uroporphyrinogen-III C-methyltransferase from Thermus thermophilus.
Related PDB1v9a,1va0
[12]
CommentsX-ray crystallography
PubMed ID17229157
JournalFEBS J
Year2007
Volume274
Pages563-73
AuthorsWada K, Harada J, Yaeda Y, Tamiaki H, Oh-Oka H, Fukuyama K
TitleCrystal structures of CbiL, a methyltransferase involved in anaerobic vitamin B biosynthesis, and CbiL in complex with S-adenosylhomocysteine - implications for the reaction mechanism.
Related PDB2e0k,2e0n

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:

createdupdated
2007-02-192009-04-03
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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