CPS_METS3
ID CPS_METS3 Reviewed; 367 AA.
AC A5UK38;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 1.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=Carbamoyl-phosphate synthase {ECO:0000255|HAMAP-Rule:MF_02221, ECO:0000305|PubMed:23107800};
DE EC=6.3.4.16 {ECO:0000255|HAMAP-Rule:MF_02221, ECO:0000269|PubMed:23107800};
DE AltName: Full=Carbamoyl phosphate synthetase {ECO:0000255|HAMAP-Rule:MF_02221, ECO:0000303|PubMed:23107800};
DE Short=CPSase {ECO:0000255|HAMAP-Rule:MF_02221, ECO:0000303|PubMed:23107800};
DE AltName: Full=SYN3 {ECO:0000303|PubMed:23107800};
GN OrderedLocusNames=Msm_0361 {ECO:0000312|EMBL:ABQ86566.1};
OS Methanobrevibacter smithii (strain ATCC 35061 / DSM 861 / OCM 144 / PS).
OC Archaea; Euryarchaeota; Methanomada group; Methanobacteria;
OC Methanobacteriales; Methanobacteriaceae; Methanobrevibacter.
OX NCBI_TaxID=420247;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 35061 / DSM 861 / OCM 144 / PS;
RX PubMed=17563350; DOI=10.1073/pnas.0704189104;
RA Samuel B.S., Hansen E.E., Manchester J.K., Coutinho P.M., Henrissat B.,
RA Fulton R., Latreille P., Kim K., Wilson R.K., Gordon J.I.;
RT "Genomic and metabolic adaptations of Methanobrevibacter smithii to the
RT human gut.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:10643-10648(2007).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT,
RP 3D-STRUCTURE MODELING, REACTION MECHANISM, AND DOMAIN.
RC STRAIN=ATCC 35061 / DSM 861 / OCM 144 / PS;
RX PubMed=23107800; DOI=10.1159/000342520;
RA Popa E., Perera N., Kibedi-Szabo C.Z., Guy-Evans H., Evans D.R.,
RA Purcarea C.;
RT "The smallest active carbamoyl phosphate synthetase was identified in the
RT human gut archaeon Methanobrevibacter smithii.";
RL J. Mol. Microbiol. Biotechnol. 22:287-299(2012).
CC -!- FUNCTION: Catalyzes the synthesis of carbamoyl phosphate from ATP,
CC ammonium and bicarbonate. Proceeds via a three-step mechanism, i.e. the
CC phosphorylation of hydrogencarbonate to carboxyphosphate, a
CC nucleophilic attack of ammonia on carboxyphosphate yielding carbamate,
CC and the phosphorylation of carbamate forming carbamoyl phosphate. In
CC M.smithii, the predominant archaeon in the human gut, one function of
CC this enzyme may be to sequester ammonia, a scarce nutrient in the
CC intestine which is the major source of nitrogen in M.smithii for the
CC biosynthesis of nucleotides, amino acids, and many other metabolites.
CC {ECO:0000269|PubMed:23107800}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 ATP + hydrogencarbonate + NH4(+) = 2 ADP + carbamoyl
CC phosphate + 2 H(+) + phosphate; Xref=Rhea:RHEA:18029,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17544, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58228,
CC ChEBI:CHEBI:456216; EC=6.3.4.16; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_02221, ECO:0000269|PubMed:23107800};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18030;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_02221,
CC ECO:0000305|PubMed:23107800};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409};
CC Note=Binds 2 magnesium or manganese ions per subunit.
CC {ECO:0000255|PROSITE-ProRule:PRU00409};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.61 mM for ATP (at 38 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:23107800};
CC KM=15.6 mM for NH4(+) (at 38 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:23107800};
CC KM=14.5 mM for hydrogencarbonate (at 38 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:23107800};
CC Vmax=62 nmol/min/mg enzyme towards ATP (at 38 degrees Celsius and pH
CC 8.0) {ECO:0000269|PubMed:23107800};
CC Vmax=75 nmol/min/mg enzyme towards NH4(+) (at 38 degrees Celsius and
CC pH 8.0) {ECO:0000269|PubMed:23107800};
CC Vmax=64 nmol/min/mg enzyme towards hydrogencarbonate (at 38 degrees
CC Celsius and pH 8.0) {ECO:0000269|PubMed:23107800};
CC Note=kcat is 0.043 sec(-1) towards ATP (at 38 degrees Celsius and pH
CC 8.0). kcat is 0.052 sec(-1) towards NH4(+) (at 38 degrees Celsius and
CC pH 8.0). kcat is 0.044 sec(-1) towards hydrogencarbonate (at 38
CC degrees Celsius and pH 8.0). {ECO:0000269|PubMed:23107800};
CC -!- SUBUNIT: Forms homodimers and homotetramers (dimers of dimers).
CC {ECO:0000269|PubMed:23107800}.
CC -!- DOMAIN: Lacks the domain involved in allosteric regulation present in
CC CarB CPSases. {ECO:0000269|PubMed:23107800}.
CC -!- MISCELLANEOUS: Several lines of evidence suggest that obesity is
CC associated with elevated levels of intestinal methanogenic archaea.
CC Consequently, this enzyme may be an attractive drug target in the
CC treatment of human obesity. {ECO:0000303|PubMed:23107800}.
CC -!- SIMILARITY: Belongs to the small carbamoyl-phosphate synthase family.
CC {ECO:0000255|HAMAP-Rule:MF_02221, ECO:0000305}.
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DR EMBL; CP000678; ABQ86566.1; -; Genomic_DNA.
DR RefSeq; WP_011953845.1; NC_009515.1.
DR AlphaFoldDB; A5UK38; -.
DR SMR; A5UK38; -.
DR STRING; 420247.Msm_0361; -.
DR EnsemblBacteria; ABQ86566; ABQ86566; Msm_0361.
DR GeneID; 5216509; -.
DR KEGG; msi:Msm_0361; -.
DR PATRIC; fig|420247.28.peg.362; -.
DR eggNOG; arCOG01596; Archaea.
DR HOGENOM; CLU_734905_0_0_2; -.
DR OMA; YQRITIR; -.
DR BioCyc; MSMI420247:GHWZ-366-MON; -.
DR BRENDA; 6.3.4.16; 11234.
DR Proteomes; UP000001992; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004087; F:carbamoyl-phosphate synthase (ammonia) activity; IEA:UniProtKB-UniRule.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0030145; F:manganese ion binding; IEA:UniProtKB-UniRule.
DR Gene3D; 3.30.1490.20; -; 1.
DR HAMAP; MF_02221; CPSase; 1.
DR InterPro; IPR011761; ATP-grasp.
DR InterPro; IPR003806; ATP-grasp_PylC-type.
DR InterPro; IPR013815; ATP_grasp_subdomain_1.
DR InterPro; IPR043673; CPSase_Archaea.
DR Pfam; PF02655; ATP-grasp_3; 1.
DR PROSITE; PS50975; ATP_GRASP; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Ligase; Magnesium; Manganese; Metal-binding;
KW Nucleotide-binding.
FT CHAIN 1..367
FT /note="Carbamoyl-phosphate synthase"
FT /id="PRO_0000448004"
FT DOMAIN 111..296
FT /note="ATP-grasp"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 137..186
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 253
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 253
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 267
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 267
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 267
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 267
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 269
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 269
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
SQ SEQUENCE 367 AA; 41403 MW; 088D98457C6E387D CRC64;
MKILFIGSRL YDDIDYYVRE NGIESIITES NEDAINLDLP DQVFIVPRGM DSPKQIAISQ
NVDAVVPLIG IDPPLIEVAK MKEELEAETD IPVIAANVRA VRLTSDKIKT KEFYNEIGVP
TPQYQILAKD DFESKLKMEF PVVLKQGQGQ GGKDIKVAES LDDVKEYFEE FDHALCEKFI
EGSEISIEVL GYNGEYVPLS PIYKGETTLE GIHPLNKIKT APCLVEGLDN NLVQRTAYKV
AKNLGSDGIF EMDFMFSKDE QQLYAIEVNT RPNGTRYLTT ATCGVNSLCE LVNMAAGKFS
IKDIQDKLEY YYATEIPIGR YKGPDLNEPL KSFKNNDWVV HGPEGYQRIT IRADSKEQLD
RYVEDLI
