CYSG_SALTY
ID CYSG_SALTY Reviewed; 457 AA.
AC P25924;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Siroheme synthase {ECO:0000255|HAMAP-Rule:MF_01646};
DE Includes:
DE RecName: Full=Uroporphyrinogen-III C-methyltransferase {ECO:0000255|HAMAP-Rule:MF_01646};
DE Short=Urogen III methylase {ECO:0000255|HAMAP-Rule:MF_01646};
DE EC=2.1.1.107 {ECO:0000269|PubMed:14595395};
DE AltName: Full=SUMT {ECO:0000255|HAMAP-Rule:MF_01646};
DE AltName: Full=Uroporphyrinogen III methylase {ECO:0000255|HAMAP-Rule:MF_01646};
DE Short=UROM {ECO:0000255|HAMAP-Rule:MF_01646};
DE Includes:
DE RecName: Full=Precorrin-2 dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01646};
DE EC=1.3.1.76 {ECO:0000269|PubMed:14595395};
DE Includes:
DE RecName: Full=Sirohydrochlorin ferrochelatase {ECO:0000255|HAMAP-Rule:MF_01646};
DE EC=4.99.1.4 {ECO:0000269|PubMed:14595395};
GN Name=cysG {ECO:0000255|HAMAP-Rule:MF_01646}; OrderedLocusNames=STM3477;
OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=99287;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1987123; DOI=10.1128/jb.173.1.325-333.1991;
RA Wu J.Y., Siegel L.M., Kredich N.M.;
RT "High-level expression of Escherichia coli NADPH-sulfite reductase:
RT requirement for a cloned cysG plasmid to overcome limiting siroheme
RT cofactor.";
RL J. Bacteriol. 173:325-333(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=11677609; DOI=10.1038/35101614;
RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P.,
RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D.,
RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E.,
RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R.,
RA Wilson R.K.;
RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.";
RL Nature 413:852-856(2001).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF WILD-TYPE AND OF MUTANT ALA-128
RP IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE AND NAD, FUNCTION, CATALYTIC
RP ACTIVITY, MUTAGENESIS OF SER-128; LEU-250; LYS-270 AND ASN-385, ACTIVE
RP SITE, SUBUNIT, AND PHOSPHORYLATION AT SER-128.
RX PubMed=14595395; DOI=10.1038/nsb1007;
RA Stroupe M.E., Leech H.K., Daniels D.S., Warren M.J., Getzoff E.D.;
RT "CysG structure reveals tetrapyrrole-binding features and novel regulation
RT of siroheme biosynthesis.";
RL Nat. Struct. Biol. 10:1064-1073(2003).
CC -!- FUNCTION: Multifunctional enzyme that catalyzes the SAM-dependent
CC methylations of uroporphyrinogen III at position C-2 and C-7 to form
CC precorrin-2 via precorrin-1. Then it catalyzes the NAD-dependent ring
CC dehydrogenation of precorrin-2 to yield sirohydrochlorin. Finally, it
CC catalyzes the ferrochelation of sirohydrochlorin to yield siroheme.
CC {ECO:0000269|PubMed:14595395}.
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:14595395};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + precorrin-2 = 2 H(+) + NADH + sirohydrochlorin;
CC Xref=Rhea:RHEA:15613, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:58351, ChEBI:CHEBI:58827; EC=1.3.1.76;
CC Evidence={ECO:0000269|PubMed:14595395};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + siroheme = Fe(2+) + sirohydrochlorin;
CC Xref=Rhea:RHEA:24360, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033,
CC ChEBI:CHEBI:58351, ChEBI:CHEBI:60052; EC=4.99.1.4;
CC Evidence={ECO:0000269|PubMed:14595395};
CC -!- PATHWAY: Cofactor biosynthesis; adenosylcobalamin biosynthesis;
CC precorrin-2 from uroporphyrinogen III: step 1/1. {ECO:0000255|HAMAP-
CC Rule:MF_01646}.
CC -!- PATHWAY: Cofactor biosynthesis; adenosylcobalamin biosynthesis;
CC sirohydrochlorin from precorrin-2: step 1/1. {ECO:0000255|HAMAP-
CC Rule:MF_01646}.
CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme
CC biosynthesis; precorrin-2 from uroporphyrinogen III: step 1/1.
CC {ECO:0000255|HAMAP-Rule:MF_01646}.
CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme
CC biosynthesis; siroheme from sirohydrochlorin: step 1/1.
CC {ECO:0000255|HAMAP-Rule:MF_01646}.
CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme
CC biosynthesis; sirohydrochlorin from precorrin-2: step 1/1.
CC {ECO:0000255|HAMAP-Rule:MF_01646}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:14595395}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the precorrin-2
CC dehydrogenase / sirohydrochlorin ferrochelatase family.
CC {ECO:0000255|HAMAP-Rule:MF_01646}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the precorrin
CC methyltransferase family. {ECO:0000255|HAMAP-Rule:MF_01646}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M64606; AAA27041.1; -; Genomic_DNA.
DR EMBL; AE006468; AAL22339.1; -; Genomic_DNA.
DR PIR; B39200; B39200.
DR RefSeq; NP_462380.1; NC_003197.2.
DR RefSeq; WP_000349895.1; NC_003197.2.
DR PDB; 1PJQ; X-ray; 2.21 A; A/B=1-457.
DR PDB; 1PJS; X-ray; 2.40 A; A/B=1-457.
DR PDB; 1PJT; X-ray; 2.80 A; A/B=1-457.
DR PDB; 6P5X; X-ray; 1.97 A; A/B=1-457.
DR PDB; 6P5Z; X-ray; 2.26 A; A/B=1-457.
DR PDB; 6P7C; X-ray; 2.76 A; A/B=1-457.
DR PDB; 6P7D; X-ray; 2.40 A; A/B=1-457.
DR PDB; 6PQZ; X-ray; 2.23 A; A/B=1-457.
DR PDB; 6PR0; X-ray; 1.90 A; A/B=1-457.
DR PDB; 6PR1; X-ray; 1.82 A; A/B=1-457.
DR PDB; 6PR2; X-ray; 2.16 A; A/B=1-457.
DR PDB; 6PR3; X-ray; 1.96 A; A/B=1-457.
DR PDB; 6PR4; X-ray; 2.24 A; A/B=1-457.
DR PDB; 6ULU; X-ray; 2.76 A; A/B=1-457.
DR PDB; 6VEB; X-ray; 2.55 A; A/B=1-457.
DR PDBsum; 1PJQ; -.
DR PDBsum; 1PJS; -.
DR PDBsum; 1PJT; -.
DR PDBsum; 6P5X; -.
DR PDBsum; 6P5Z; -.
DR PDBsum; 6P7C; -.
DR PDBsum; 6P7D; -.
DR PDBsum; 6PQZ; -.
DR PDBsum; 6PR0; -.
DR PDBsum; 6PR1; -.
DR PDBsum; 6PR2; -.
DR PDBsum; 6PR3; -.
DR PDBsum; 6PR4; -.
DR PDBsum; 6ULU; -.
DR PDBsum; 6VEB; -.
DR AlphaFoldDB; P25924; -.
DR SMR; P25924; -.
DR STRING; 99287.STM3477; -.
DR DrugBank; DB04522; Dexfosfoserine.
DR DrugBank; DB01752; S-adenosyl-L-homocysteine.
DR iPTMnet; P25924; -.
DR PaxDb; P25924; -.
DR EnsemblBacteria; AAL22339; AAL22339; STM3477.
DR GeneID; 1255000; -.
DR KEGG; stm:STM3477; -.
DR PATRIC; fig|99287.12.peg.3675; -.
DR HOGENOM; CLU_011276_2_0_6; -.
DR OMA; GRFMAQE; -.
DR PhylomeDB; P25924; -.
DR BioCyc; MetaCyc:STM3477-MON; -.
DR BioCyc; SENT99287:STM3477-MON; -.
DR UniPathway; UPA00148; UER00211.
DR UniPathway; UPA00148; UER00222.
DR UniPathway; UPA00262; UER00211.
DR UniPathway; UPA00262; UER00222.
DR UniPathway; UPA00262; UER00376.
DR EvolutionaryTrace; P25924; -.
DR PRO; PR:P25924; -.
DR Proteomes; UP000001014; Chromosome.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0043115; F:precorrin-2 dehydrogenase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0051266; F:sirohydrochlorin ferrochelatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004851; F:uroporphyrin-III C-methyltransferase activity; IBA:GO_Central.
DR GO; GO:0009236; P:cobalamin biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0019354; P:siroheme biosynthetic process; IBA:GO_Central.
DR CDD; cd11642; SUMT; 1.
DR Gene3D; 1.10.8.210; -; 1.
DR Gene3D; 3.30.950.10; -; 1.
DR Gene3D; 3.40.1010.10; -; 1.
DR HAMAP; MF_01646; Siroheme_synth; 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; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR037115; Sirohaem_synt_dimer_dom_sf.
DR InterPro; IPR012409; Sirohaem_synth.
DR InterPro; IPR028281; Sirohaem_synthase_central.
DR InterPro; IPR019478; Sirohaem_synthase_dimer_dom.
DR InterPro; IPR006367; Sirohaem_synthase_N.
DR InterPro; IPR003043; Uropor_MeTrfase_CS.
DR Pfam; PF10414; CysG_dimeriser; 1.
DR Pfam; PF14824; Sirohm_synth_M; 1.
DR Pfam; PF00590; TP_methylase; 1.
DR PIRSF; PIRSF036426; Sirohaem_synth; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53790; SSF53790; 1.
DR TIGRFAMs; TIGR01469; cobA_cysG_Cterm; 1.
DR TIGRFAMs; TIGR01470; cysG_Nterm; 1.
DR PROSITE; PS00839; SUMT_1; 1.
DR PROSITE; PS00840; SUMT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cobalamin biosynthesis; Lyase; Methyltransferase;
KW Multifunctional enzyme; NAD; Oxidoreductase; Phosphoprotein;
KW Porphyrin biosynthesis; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..457
FT /note="Siroheme synthase"
FT /id="PRO_0000150380"
FT REGION 4..202
FT /note="Precorrin-2 dehydrogenase /sirohydrochlorin
FT ferrochelatase"
FT REGION 216..448
FT /note="Uroporphyrinogen-III C-methyltransferase"
FT ACT_SITE 248
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:14595395"
FT ACT_SITE 270
FT /note="Proton donor"
FT /evidence="ECO:0000269|PubMed:14595395"
FT BINDING 22..23
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:14595395"
FT BINDING 43..44
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:14595395"
FT BINDING 225
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14595395"
FT BINDING 301..303
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14595395"
FT BINDING 306
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14595395"
FT BINDING 331..332
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14595395"
FT BINDING 382
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14595395"
FT BINDING 411
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14595395"
FT BINDING 437
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:14595395"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:14595395"
FT MUTAGEN 128
FT /note="S->A: Abolishes the methyltransferase activity and
FT increases 3 and 4-fold the dehydrogenase and ferrochelatase
FT activities, respectively."
FT /evidence="ECO:0000269|PubMed:14595395"
FT MUTAGEN 128
FT /note="S->D: Abolishes the methyltransferase activity and
FT reduces 10 and 5-fold the dehydrogenase and ferrochelatase
FT activities, respectively."
FT /evidence="ECO:0000269|PubMed:14595395"
FT MUTAGEN 250
FT /note="L->A: Abolishes the dehydrogenase and ferrochelatase
FT activities and reduces 6-fold the methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:14595395"
FT MUTAGEN 270
FT /note="K->I: Abolishes the methyltransferase, dehydrogenase
FT and ferrochelatase activities."
FT /evidence="ECO:0000269|PubMed:14595395"
FT MUTAGEN 385
FT /note="N->A: Abolishes the dehydrogenase and ferrochelatase
FT activities and reduces 10-fold the methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:14595395"
FT STRAND 4..8
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 14..18
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 22..33
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 37..44
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 47..54
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 57..64
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 67..70
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 74..78
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 83..94
FT /evidence="ECO:0007829|PDB:6PR1"
FT TURN 95..97
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 99..102
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 108..112
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 115..119
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 122..127
FT /evidence="ECO:0007829|PDB:6PR1"
FT TURN 129..131
FT /evidence="ECO:0007829|PDB:6PQZ"
FT HELIX 133..144
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 151..168
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 172..182
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 186..193
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 197..209
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 217..222
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 228..230
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 233..241
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 243..247
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 253..256
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 271..273
FT /evidence="ECO:0007829|PDB:1PJS"
FT HELIX 279..291
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 295..302
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 310..315
FT /evidence="ECO:0007829|PDB:6PR1"
FT TURN 316..321
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 324..327
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 332..340
FT /evidence="ECO:0007829|PDB:6PR1"
FT TURN 347..349
FT /evidence="ECO:0007829|PDB:6PR3"
FT STRAND 351..358
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:1PJQ"
FT HELIX 368..371
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 374..382
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 384..386
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 387..396
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 404..410
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 417..422
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 423..425
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 426..430
FT /evidence="ECO:0007829|PDB:6PR1"
FT STRAND 435..442
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 443..447
FT /evidence="ECO:0007829|PDB:6PR1"
FT HELIX 448..451
FT /evidence="ECO:0007829|PDB:6PR1"
SQ SEQUENCE 457 AA; 50147 MW; 359C8CAF4B78092D CRC64;
MDHLPIFCQL RDRDCLIVGG GDVAERKARL LLEAGARLTV NALTFIPQFT VWANEGMLTL
VEGPFDETLL DSCWLAIAAT DDDTVNQRVS DAAESRRIFC NVVDAPKAAS FIMPSIIDRS
PLMVAVSSGG TSPVLARLLR EKLESLLPQH LGQVARYAGQ LRARVKKQFA TMGERRRFWE
KFFVNDRLAQ SLANADEKAV NATTERLFSE PLDHRGEVVL VGAGPGDAGL LTLKGLQQIQ
QADIVVYDRL VSDDIMNLVR RDADRVFVGK RAGYHCVPQE EINQILLREA QKGKRVVRLK
GGDPFIFGRG GEELETLCHA GIPFSVVPGI TAASGCSAYS GIPLTHRDYA QSVRLVTGHL
KTGGELDWEN LAAEKQTLVF YMGLNQAATI QEKLIAFGMQ ADMPVALVEN GTSVKQRVVH
GVLTQLGELA QQVESPALII VGRVVALRDK LNWFSNH
