CYSG_NEIMB
ID CYSG_NEIMB Reviewed; 483 AA.
AC P95370; Q9JQK6;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 3.
DT 03-AUG-2022, entry version 149.
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:0000255|HAMAP-Rule:MF_01646};
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:0000255|HAMAP-Rule:MF_01646};
DE Includes:
DE RecName: Full=Sirohydrochlorin ferrochelatase {ECO:0000255|HAMAP-Rule:MF_01646};
DE EC=4.99.1.4 {ECO:0000255|HAMAP-Rule:MF_01646};
GN Name=cysG {ECO:0000255|HAMAP-Rule:MF_01646}; Synonyms=cysG1;
GN OrderedLocusNames=NMB1156;
GN and
GN Name=cysG2 {ECO:0000255|HAMAP-Rule:MF_01646}; OrderedLocusNames=NMB1194;
OS Neisseria meningitidis serogroup B (strain MC58).
OC Bacteria; Proteobacteria; Betaproteobacteria; Neisseriales; Neisseriaceae;
OC Neisseria.
OX NCBI_TaxID=122586;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=MC58;
RA McVeigh T., Wilkie S.E., Woodcock S.C., Mortuza G., Peters S.E.,
RA Warren M.J.;
RT "Sirohaem synthase from Neisseria meningitidis.";
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MC58;
RX PubMed=10710307; DOI=10.1126/science.287.5459.1809;
RA Tettelin H., Saunders N.J., Heidelberg J.F., Jeffries A.C., Nelson K.E.,
RA Eisen J.A., Ketchum K.A., Hood D.W., Peden J.F., Dodson R.J., Nelson W.C.,
RA Gwinn M.L., DeBoy R.T., Peterson J.D., Hickey E.K., Haft D.H.,
RA Salzberg S.L., White O., Fleischmann R.D., Dougherty B.A., Mason T.M.,
RA Ciecko A., Parksey D.S., Blair E., Cittone H., Clark E.B., Cotton M.D.,
RA Utterback T.R., Khouri H.M., Qin H., Vamathevan J.J., Gill J., Scarlato V.,
RA Masignani V., Pizza M., Grandi G., Sun L., Smith H.O., Fraser C.M.,
RA Moxon E.R., Rappuoli R., Venter J.C.;
RT "Complete genome sequence of Neisseria meningitidis serogroup B strain
RT MC58.";
RL Science 287:1809-1815(2000).
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:0000255|HAMAP-Rule:MF_01646}.
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:0000255|HAMAP-Rule:MF_01646};
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:0000255|HAMAP-Rule:MF_01646};
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:0000255|HAMAP-Rule:MF_01646};
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 -!- 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}.
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DR EMBL; Y10177; CAA71251.1; -; Genomic_DNA.
DR EMBL; AE002098; AAF41542.1; -; Genomic_DNA.
DR EMBL; AE002098; AAF41577.1; -; Genomic_DNA.
DR PIR; D81111; D81111.
DR PIR; T46867; T46867.
DR RefSeq; NP_274184.1; NC_003112.2.
DR RefSeq; NP_274220.1; NC_003112.2.
DR RefSeq; WP_002225211.1; NC_003112.2.
DR AlphaFoldDB; P95370; -.
DR SMR; P95370; -.
DR STRING; 122586.NMB1156; -.
DR PaxDb; P95370; -.
DR EnsemblBacteria; AAF41542; AAF41542; NMB1156.
DR EnsemblBacteria; AAF41577; AAF41577; NMB1194.
DR KEGG; nme:NMB1156; -.
DR KEGG; nme:NMB1194; -.
DR PATRIC; fig|122586.8.peg.1461; -.
DR HOGENOM; CLU_011276_2_0_4; -.
DR OMA; KMTVVVY; -.
DR UniPathway; UPA00148; UER00211.
DR UniPathway; UPA00148; UER00222.
DR UniPathway; UPA00262; UER00211.
DR UniPathway; UPA00262; UER00222.
DR UniPathway; UPA00262; UER00376.
DR Proteomes; UP000000425; Chromosome.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0043115; F:precorrin-2 dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0051266; F:sirohydrochlorin ferrochelatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004851; F:uroporphyrin-III C-methyltransferase activity; IEA:UniProtKB-UniRule.
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 3: Inferred from homology;
KW Cobalamin biosynthesis; Lyase; Methyltransferase; Multifunctional enzyme;
KW NAD; Oxidoreductase; Phosphoprotein; Porphyrin biosynthesis;
KW Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..483
FT /note="Siroheme synthase"
FT /id="PRO_0000150382"
FT REGION 1..203
FT /note="Precorrin-2 dehydrogenase /sirohydrochlorin
FT ferrochelatase"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646"
FT REGION 217..483
FT /note="Uroporphyrinogen-III C-methyltransferase"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646"
FT ACT_SITE 249
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646"
FT ACT_SITE 271
FT /note="Proton donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646"
FT BINDING 22..23
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646"
FT BINDING 43..44
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646"
FT BINDING 226
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646"
FT BINDING 302..304
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646"
FT BINDING 307
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646"
FT BINDING 332..333
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646"
FT BINDING 384
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646"
FT BINDING 413
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01646"
FT CONFLICT 475..483
FT /note="GLNAGQRAA -> D (in Ref. 1; CAA71251)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 483 AA; 52111 MW; 279C4F458B19582F CRC64;
MNYFPIFANL AGRPVLVVGG GAVAARKISL LLKAGAEVRV AAKHLNAELS ALAAENKILW
LAEEFRAEHI RTVFLIIAAS SDQALNRRVF HLAESCQKPV NVVDDRDHCS FIFPSVIDRN
PVQIAVSSSG SAPVLARLLR ERLEALLPPS LGDMAEISGR WRDAVKGKLK SVTERRRFWE
KQFNGRFAAL VKNRQNTLAE RELAGQLEQS RQNDQGGSVS LVGAGPGDAG LLTLKGLQEI
QQADVVLYDA LVSDGILSLV RRDAERIFVG KRARGERTPQ EDTNALMVRL AREGRRVVRL
KGGDPFVFGR GGEELETLAR HQIPFSVVPG ITAAVGATAY AGIPLTHRDY AQSAVFVTGH
RKADAPDIEW QTLARSRQTL VIYMGALKAA LIAERLQQHG RSPDTPAAVI SQGTLPAQKT
ATGTLANLAE LAETAPNPAL IVIGEVVGLH EKLAWFGENG EGENRVGQTY PALGGLNAGQ
RAA
