SUMT_SINSX
ID SUMT_SINSX Reviewed; 280 AA.
AC P21631;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Uroporphyrinogen-III C-methyltransferase {ECO:0000305|PubMed:2546914};
DE Short=Urogen III methylase;
DE EC=2.1.1.107 {ECO:0000269|PubMed:2546914};
DE AltName: Full=S-adenosyl-L-methionine:uroporphyrinogen III methyltransferase {ECO:0000303|PubMed:2546914};
DE Short=SUMT {ECO:0000303|PubMed:2546914};
DE AltName: Full=Uroporphyrinogen III methylase;
DE Short=UROM;
GN Name=cobA {ECO:0000312|EMBL:AAA25773.1};
OS Sinorhizobium sp.
OC Bacteria; Proteobacteria; Alphaproteobacteria; Hyphomicrobiales;
OC Rhizobiaceae; Sinorhizobium/Ensifer group; Sinorhizobium.
OX NCBI_TaxID=42445;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 1-10.
RC STRAIN=SC510;
RX PubMed=2211520; DOI=10.1128/jb.172.10.5968-5979.1990;
RA Crouzet J., Cauchois L., Blanche F., Debussche L., Thibaut D.,
RA Rouyez M.-C., Rigault S., Mayaux J.-F., Cameron B.;
RT "Nucleotide sequence of a Pseudomonas denitrificans 5.4-kilobase DNA
RT fragment containing five cob genes and identification of structural genes
RT encoding S-adenosyl-L-methionine: uroporphyrinogen III methyltransferase
RT and cobyrinic acid a,c-diamide synthase.";
RL J. Bacteriol. 172:5968-5979(1990).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, ACTIVITY REGULATION, SUBUNIT, DISRUPTION PHENOTYPE, AND
RP PATHWAY.
RX PubMed=2546914; DOI=10.1128/jb.171.8.4222-4231.1989;
RA Blanche F., Debussche L., Thibaut D., Crouzet J., Cameron B.;
RT "Purification and characterization of S-adenosyl-L-methionine:
RT uroporphyrinogen III methyltransferase from Pseudomonas denitrificans.";
RL J. Bacteriol. 171:4222-4231(1989).
RN [3] {ECO:0007744|PDB:1S4D}
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE, SUBUNIT, AND MUTAGENESIS OF ASP-47; LEU-49;
RP PHE-106; THR-130; TYR-183 AND MET-184.
RX PubMed=15522295; DOI=10.1016/j.jmb.2004.09.020;
RA Vevodova J., Graham R.M., Raux E., Schubert H.L., Roper D.I.,
RA Brindley A.A., Ian Scott A., Roessner C.A., Stamford N.P.J., Stroupe M.E.,
RA Getzoff E.D., Warren M.J., Wilson K.S.;
RT "Structure/function studies on a S-adenosyl-L-methionine-dependent
RT uroporphyrinogen III C methyltransferase (SUMT), a key regulatory enzyme of
RT tetrapyrrole biosynthesis.";
RL J. Mol. Biol. 344:419-433(2004).
CC -!- FUNCTION: Catalyzes the two successive C-2 and C-7 methylation
CC reactions involved in the conversion of uroporphyrinogen III to
CC precorrin-2 via the intermediate formation of precorrin-1. It is a step
CC in the biosynthesis of both cobalamin (vitamin B12) and siroheme.
CC Neither uroporphyrin III nor the chlorin (factor I) is a substrate of
CC SUMT. {ECO:0000269|PubMed:2546914}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 S-adenosyl-L-methionine + uroporphyrinogen III = H(+) +
CC precorrin-2 + 2 S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:32459,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57308, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:58827, ChEBI:CHEBI:59789; EC=2.1.1.107;
CC Evidence={ECO:0000269|PubMed:2546914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32460;
CC Evidence={ECO:0000305|PubMed:2546914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-adenosyl-L-methionine + uroporphyrinogen III = H(+) +
CC precorrin-1 + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:19089,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57308, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:58893, ChEBI:CHEBI:59789;
CC Evidence={ECO:0000269|PubMed:2546914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19090;
CC Evidence={ECO:0000305|PubMed:2546914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=precorrin-1 + S-adenosyl-L-methionine = precorrin-2 + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:21972, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:58827, ChEBI:CHEBI:58893, ChEBI:CHEBI:59789;
CC Evidence={ECO:0000269|PubMed:2546914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21973;
CC Evidence={ECO:0000305|PubMed:2546914};
CC -!- ACTIVITY REGULATION: S-adenosylhomocysteine is an extremely powerful
CC competitive inhibitor of the uroporphyrinogen III methylation. SUMT
CC exhibits a substrate inhibition phenomenon at uroporphyrinogen III
CC concentrations above 2 uM; this property might play a regulatory role
CC in cobalamin biosynthesis. The enzyme activity is completely
CC insensitive to feedback inhibition by cobalamin and corrinoid
CC intermediates. {ECO:0000269|PubMed:2546914}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.3 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:2546914};
CC KM=1.0 uM for uroporphyrinogen III {ECO:0000269|PubMed:2546914};
CC Vmax=640 nmol/h/mg enzyme {ECO:0000269|PubMed:2546914};
CC Note=kcat is 38 h(-1). {ECO:0000269|PubMed:2546914};
CC pH dependence:
CC Optimum pH is 7.7. {ECO:0000269|PubMed:2546914};
CC -!- PATHWAY: Cofactor biosynthesis; adenosylcobalamin biosynthesis;
CC precorrin-2 from uroporphyrinogen III: step 1/1.
CC {ECO:0000269|PubMed:2546914}.
CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme
CC biosynthesis; precorrin-2 from uroporphyrinogen III: step 1/1.
CC {ECO:0000305|PubMed:2546914}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15522295,
CC ECO:0000269|PubMed:2546914}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene are deficient in
CC cobalamin biosynthesis. {ECO:0000269|PubMed:2546914}.
CC -!- MISCELLANEOUS: Uroporphyrinogen III is a key intermediate because of
CC its position at the branch point of two divergent pathways. One pathway
CC leads to protoheme, and the other one is the cobalamin and siroheme
CC pathway. {ECO:0000305|PubMed:2546914}.
CC -!- SIMILARITY: Belongs to the precorrin methyltransferase family.
CC {ECO:0000305}.
CC -!- CAUTION: Was originally thought to originate from Pseudomonas
CC denitrificans, but similarity searches show that the sequence is much
CC closer to Sinorhizobium. The entry's taxonomy has been changed.
CC {ECO:0000305}.
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DR EMBL; M59236; AAA25773.1; -; Genomic_DNA.
DR PDB; 1S4D; X-ray; 2.70 A; A/B/D/E/F/G/H/I/J/K/L/M=1-280.
DR PDBsum; 1S4D; -.
DR AlphaFoldDB; P21631; -.
DR SMR; P21631; -.
DR DrugBank; DB01752; S-adenosyl-L-homocysteine.
DR BioCyc; MetaCyc:MON-82; -.
DR UniPathway; UPA00148; UER00211.
DR UniPathway; UPA00262; UER00211.
DR EvolutionaryTrace; P21631; -.
DR GO; GO:0004851; F:uroporphyrin-III C-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0009236; P:cobalamin biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0019354; P:siroheme biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd11642; SUMT; 1.
DR Gene3D; 3.30.950.10; -; 1.
DR Gene3D; 3.40.1010.10; -; 1.
DR InterPro; IPR000878; 4pyrrol_Mease.
DR InterPro; IPR035996; 4pyrrol_Methylase_sf.
DR InterPro; IPR014777; 4pyrrole_Mease_sub1.
DR InterPro; IPR014776; 4pyrrole_Mease_sub2.
DR InterPro; IPR006366; CobA/CysG_C.
DR InterPro; IPR003043; Uropor_MeTrfase_CS.
DR Pfam; PF00590; TP_methylase; 1.
DR SUPFAM; SSF53790; SSF53790; 1.
DR TIGRFAMs; TIGR01469; cobA_cysG_Cterm; 1.
DR PROSITE; PS00839; SUMT_1; 1.
DR PROSITE; PS00840; SUMT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cobalamin biosynthesis; Direct protein sequencing;
KW Methyltransferase; Porphyrin biosynthesis; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..280
FT /note="Uroporphyrinogen-III C-methyltransferase"
FT /id="PRO_0000150372"
FT BINDING 24
FT /ligand="S-adenosyl-L-homocysteine"
FT /ligand_id="ChEBI:CHEBI:57856"
FT /evidence="ECO:0000269|PubMed:15522295,
FT ECO:0007744|PDB:1S4D"
FT BINDING 100..102
FT /ligand="S-adenosyl-L-homocysteine"
FT /ligand_id="ChEBI:CHEBI:57856"
FT /evidence="ECO:0000269|PubMed:15522295,
FT ECO:0007744|PDB:1S4D"
FT BINDING 130..131
FT /ligand="S-adenosyl-L-homocysteine"
FT /ligand_id="ChEBI:CHEBI:57856"
FT /evidence="ECO:0000269|PubMed:15522295,
FT ECO:0007744|PDB:1S4D"
FT BINDING 184
FT /ligand="S-adenosyl-L-homocysteine"
FT /ligand_id="ChEBI:CHEBI:57856"
FT /evidence="ECO:0000269|PubMed:15522295,
FT ECO:0007744|PDB:1S4D"
FT BINDING 213
FT /ligand="S-adenosyl-L-homocysteine"
FT /ligand_id="ChEBI:CHEBI:57856"
FT /evidence="ECO:0000269|PubMed:15522295,
FT ECO:0007744|PDB:1S4D"
FT BINDING 241
FT /ligand="S-adenosyl-L-homocysteine"
FT /ligand_id="ChEBI:CHEBI:57856"
FT /evidence="ECO:0000269|PubMed:15522295,
FT ECO:0007744|PDB:1S4D"
FT MUTAGEN 47
FT /note="D->N: Reduces S-adenosyl-L-methionine binding by
FT about 75%. Causes accumulation of precorrin-1."
FT /evidence="ECO:0000269|PubMed:15522295"
FT MUTAGEN 49
FT /note="L->A: Reduces S-adenosyl-L-methionine binding by
FT about 50%. Causes slow synthesis of precorrin-2 and
FT accumulation of precorrin-1."
FT /evidence="ECO:0000269|PubMed:15522295"
FT MUTAGEN 106
FT /note="F->A: Strongly reduces S-adenosyl-L-methionine
FT binding. Loss of activity."
FT /evidence="ECO:0000269|PubMed:15522295"
FT MUTAGEN 130
FT /note="T->A: Strongly reduces S-adenosyl-L-methionine
FT binding. Causes slow synthesis of precorrin-2."
FT /evidence="ECO:0000269|PubMed:15522295"
FT MUTAGEN 183
FT /note="Y->A: Strongly reduces S-adenosyl-L-methionine
FT binding. Loss of activity."
FT /evidence="ECO:0000269|PubMed:15522295"
FT MUTAGEN 184
FT /note="M->A: Strongly reduces S-adenosyl-L-methionine
FT binding. Causes drastic effects on enzyme activity."
FT /evidence="ECO:0000269|PubMed:15522295"
FT STRAND 17..21
FT /evidence="ECO:0007829|PDB:1S4D"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:1S4D"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:1S4D"
FT HELIX 32..40
FT /evidence="ECO:0007829|PDB:1S4D"
FT STRAND 42..46
FT /evidence="ECO:0007829|PDB:1S4D"
FT HELIX 54..57
FT /evidence="ECO:0007829|PDB:1S4D"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:1S4D"
FT HELIX 78..90
FT /evidence="ECO:0007829|PDB:1S4D"
FT STRAND 95..101
FT /evidence="ECO:0007829|PDB:1S4D"
FT STRAND 105..108
FT /evidence="ECO:0007829|PDB:1S4D"
FT HELIX 109..117
FT /evidence="ECO:0007829|PDB:1S4D"
FT TURN 118..120
FT /evidence="ECO:0007829|PDB:1S4D"
FT STRAND 123..126
FT /evidence="ECO:0007829|PDB:1S4D"
FT TURN 131..133
FT /evidence="ECO:0007829|PDB:1S4D"
FT HELIX 134..138
FT /evidence="ECO:0007829|PDB:1S4D"
FT TURN 146..148
FT /evidence="ECO:0007829|PDB:1S4D"
FT STRAND 150..156
FT /evidence="ECO:0007829|PDB:1S4D"
FT HELIX 170..174
FT /evidence="ECO:0007829|PDB:1S4D"
FT STRAND 178..184
FT /evidence="ECO:0007829|PDB:1S4D"
FT HELIX 189..198
FT /evidence="ECO:0007829|PDB:1S4D"
FT STRAND 206..212
FT /evidence="ECO:0007829|PDB:1S4D"
FT STRAND 219..224
FT /evidence="ECO:0007829|PDB:1S4D"
FT TURN 225..227
FT /evidence="ECO:0007829|PDB:1S4D"
FT HELIX 228..235
FT /evidence="ECO:0007829|PDB:1S4D"
FT STRAND 239..246
FT /evidence="ECO:0007829|PDB:1S4D"
FT HELIX 247..251
FT /evidence="ECO:0007829|PDB:1S4D"
FT HELIX 252..255
FT /evidence="ECO:0007829|PDB:1S4D"
FT HELIX 257..261
FT /evidence="ECO:0007829|PDB:1S4D"
SQ SEQUENCE 280 AA; 29253 MW; 3D593C535CF0610E CRC64;
MIDDLFAGLP ALEKGSVWLV GAGPGDPGLL TLHAANALRQ ADVIVHDALV NEDCLKLARP
GAVLEFAGKR GGKPSPKQRD ISLRLVELAR AGNRVLRLKG GDPFVFGRGG EEALTLVEHQ
VPFRIVPGIT AGIGGLAYAG IPVTHREVNH AVTFLTGHDS SGLVPDRINW QGIASGSPVI
VMYMAMKHIG AITANLIAGG RSPDEPVAFV CNAATPQQAV LETTLARAEA DVAAAGLEPP
AIVVVGEVVR LRAALDWIGA LDGRKLAADP FANRILRNPA
