PYRE_SALTY
ID PYRE_SALTY Reviewed; 213 AA.
AC P08870;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Orotate phosphoribosyltransferase {ECO:0000255|HAMAP-Rule:MF_01208};
DE Short=OPRT {ECO:0000255|HAMAP-Rule:MF_01208};
DE Short=OPRTase {ECO:0000255|HAMAP-Rule:MF_01208};
DE EC=2.4.2.10 {ECO:0000255|HAMAP-Rule:MF_01208};
GN Name=pyrE {ECO:0000303|PubMed:3882417}; OrderedLocusNames=STM3733;
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=8487307; DOI=10.1006/jmbi.1993.1244;
RA Scapin G., Sacchettini J.C., Dessen A., Bhatia M., Grubmeyer C.;
RT "Primary structure and crystallization of orotate phosphoribosyltransferase
RT from Salmonella typhimurium.";
RL J. Mol. Biol. 230:1304-1308(1993).
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-60.
RX PubMed=3882417; DOI=10.1111/j.1432-1033.1985.tb08693.x;
RA Neuhard J., Stauning E., Kelln R.A.;
RT "Cloning and characterization of the pyrE gene and of PyrE::Mud1 (Ap lac)
RT fusions from Salmonella typhimurium.";
RL Eur. J. Biochem. 146:597-603(1985).
RN [4]
RP PROTEIN SEQUENCE OF 2-17, FUNCTION, AND KINETIC MECHANISM.
RX PubMed=2271660; DOI=10.1021/bi00498a009;
RA Bhatia M.B., Vinitsky A., Grubmeyer C.;
RT "Kinetic mechanism of orotate phosphoribosyltransferase from Salmonella
RT typhimurium.";
RL Biochemistry 29:10480-10487(1990).
RN [5]
RP COFACTOR.
RX PubMed=7685580; DOI=10.1006/abbi.1993.1290;
RA Bhatia M.B., Grubmeyer C.;
RT "The role of divalent magnesium in activating the reaction catalyzed by
RT orotate phosphoribosyltransferase.";
RL Arch. Biochem. Biophys. 303:321-325(1993).
RN [6]
RP PROTEIN SEQUENCE OF 20-29 AND 100-108.
RX PubMed=8376388; DOI=10.1016/s0021-9258(20)80728-5;
RA Grubmeyer C., Segura E., Dorfman R.H.;
RT "Active site lysines in orotate phosphoribosyltransferase.";
RL J. Biol. Chem. 268:20299-20304(1993).
RN [7]
RP MUTAGENESIS, AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=7545005; DOI=10.1021/bi00034a007;
RA Ozturk D.H., Dorfman R.H., Scapin G., Sacchettini J.C., Grubmeyer C.;
RT "Locations and functional roles of conserved lysine residues in Salmonella
RT typhimurium orotate phosphoribosyltransferase.";
RL Biochemistry 34:10755-10763(1995).
RN [8]
RP SUBUNIT, AND BINDING SITES.
RX PubMed=7545006; DOI=10.1021/bi00034a008;
RA Ozturk D.H., Dorfman R.H., Scapin G., Sacchettini J.C., Grubmeyer C.;
RT "Structure and function of Salmonella typhimurium orotate
RT phosphoribosyltransferase: protein complementation reveals shared active
RT sites.";
RL Biochemistry 34:10764-10770(1995).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH OMP.
RX PubMed=8312245; DOI=10.1021/bi00172a001;
RA Scapin G., Grubmeyer C., Sacchettini J.C.;
RT "Crystal structure of orotate phosphoribosyltransferase.";
RL Biochemistry 33:1287-1294(1994).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH OROTATE AND PRPP.
RX PubMed=7545004; DOI=10.1021/bi00034a006;
RA Scapin G., Ozturk D.H., Grubmeyer C., Sacchettini J.C.;
RT "The crystal structure of the orotate phosphoribosyltransferase complexed
RT with orotate and alpha-D-5-phosphoribosyl-1-pyrophosphate.";
RL Biochemistry 34:10744-10754(1995).
CC -!- FUNCTION: Catalyzes the transfer of a ribosyl phosphate group from 5-
CC phosphoribose 1-diphosphate to orotate, leading to the formation of
CC orotidine monophosphate (OMP). {ECO:0000255|HAMAP-Rule:MF_01208,
CC ECO:0000269|PubMed:2271660}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diphosphate + orotidine 5'-phosphate = 5-phospho-alpha-D-
CC ribose 1-diphosphate + orotate; Xref=Rhea:RHEA:10380,
CC ChEBI:CHEBI:30839, ChEBI:CHEBI:33019, ChEBI:CHEBI:57538,
CC ChEBI:CHEBI:58017; EC=2.4.2.10; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_01208};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:7685580};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:7685580};
CC Note=Mg(2+). Mn(2+) can replace Mg(2+) as the divalent metal. The role
CC of the metal is to bind 5-phosphoribose 1-diphosphate and form a Mg-5-
CC phosphoribose 1-diphosphate complex which then serves as substrate for
CC OPRTase. {ECO:0000269|PubMed:7685580};
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC UMP from orotate: step 1/2. {ECO:0000255|HAMAP-Rule:MF_01208}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:7545004,
CC ECO:0000269|PubMed:7545006, ECO:0000269|PubMed:8312245}.
CC -!- SIMILARITY: Belongs to the purine/pyrimidine phosphoribosyltransferase
CC family. PyrE subfamily. {ECO:0000255|HAMAP-Rule:MF_01208}.
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DR EMBL; Z19547; CAA79607.1; -; Genomic_DNA.
DR EMBL; AE006468; AAL22592.1; -; Genomic_DNA.
DR PIR; S32801; S32801.
DR RefSeq; NP_462633.1; NC_003197.2.
DR RefSeq; WP_000806167.1; NC_003197.2.
DR PDB; 1LH0; X-ray; 2.00 A; A/B=1-213.
DR PDB; 1OPR; X-ray; 2.30 A; A=1-213.
DR PDB; 1STO; X-ray; 2.60 A; A=1-213.
DR PDBsum; 1LH0; -.
DR PDBsum; 1OPR; -.
DR PDBsum; 1STO; -.
DR AlphaFoldDB; P08870; -.
DR SMR; P08870; -.
DR STRING; 99287.STM3733; -.
DR DrugBank; DB01632; 5-O-phosphono-alpha-D-ribofuranosyl diphosphate.
DR DrugBank; DB02262; Orotic acid.
DR PaxDb; P08870; -.
DR EnsemblBacteria; AAL22592; AAL22592; STM3733.
DR GeneID; 1255257; -.
DR KEGG; stm:STM3733; -.
DR PATRIC; fig|99287.12.peg.3949; -.
DR HOGENOM; CLU_074878_0_1_6; -.
DR OMA; MKAYQRQ; -.
DR PhylomeDB; P08870; -.
DR BioCyc; SENT99287:STM3733-MON; -.
DR SABIO-RK; P08870; -.
DR UniPathway; UPA00070; UER00119.
DR EvolutionaryTrace; P08870; -.
DR PHI-base; PHI:7662; -.
DR Proteomes; UP000001014; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004588; F:orotate phosphoribosyltransferase activity; IBA:GO_Central.
DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; IBA:GO_Central.
DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006221; P:pyrimidine nucleotide biosynthetic process; IBA:GO_Central.
DR GO; GO:0046132; P:pyrimidine ribonucleoside biosynthetic process; IBA:GO_Central.
DR CDD; cd06223; PRTases_typeI; 1.
DR Gene3D; 3.40.50.2020; -; 1.
DR HAMAP; MF_01208; PyrE; 1.
DR InterPro; IPR023031; OPRT.
DR InterPro; IPR004467; Or_phspho_trans_dom.
DR InterPro; IPR000836; PRibTrfase_dom.
DR InterPro; IPR029057; PRTase-like.
DR Pfam; PF00156; Pribosyltran; 1.
DR SUPFAM; SSF53271; SSF53271; 1.
DR TIGRFAMs; TIGR00336; pyrE; 1.
DR PROSITE; PS00103; PUR_PYR_PR_TRANSFER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Glycosyltransferase; Magnesium;
KW Pyrimidine biosynthesis; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:2271660"
FT CHAIN 2..213
FT /note="Orotate phosphoribosyltransferase"
FT /id="PRO_0000110734"
FT BINDING 26
FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate"
FT /ligand_id="ChEBI:CHEBI:58017"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:7545004"
FT BINDING 34..35
FT /ligand="orotate"
FT /ligand_id="ChEBI:CHEBI:30839"
FT /evidence="ECO:0000269|PubMed:7545004"
FT BINDING 72..73
FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate"
FT /ligand_id="ChEBI:CHEBI:58017"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:7545004"
FT BINDING 99
FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate"
FT /ligand_id="ChEBI:CHEBI:58017"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:7545004"
FT BINDING 100
FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate"
FT /ligand_id="ChEBI:CHEBI:58017"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:7545004"
FT BINDING 103
FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate"
FT /ligand_id="ChEBI:CHEBI:58017"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:7545004"
FT BINDING 105
FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate"
FT /ligand_id="ChEBI:CHEBI:58017"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:7545004"
FT BINDING 124..132
FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate"
FT /ligand_id="ChEBI:CHEBI:58017"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:7545004"
FT BINDING 128
FT /ligand="orotate"
FT /ligand_id="ChEBI:CHEBI:30839"
FT /evidence="ECO:0000269|PubMed:7545004"
FT BINDING 156
FT /ligand="orotate"
FT /ligand_id="ChEBI:CHEBI:30839"
FT /evidence="ECO:0000269|PubMed:7545004"
FT MUTAGEN 19
FT /note="K->Q: No loss of activity."
FT /evidence="ECO:0000269|PubMed:7545005"
FT MUTAGEN 26
FT /note="K->A,Q: Reduced activity."
FT /evidence="ECO:0000269|PubMed:7545005"
FT MUTAGEN 73
FT /note="K->A,Q: Significant loss of activity."
FT /evidence="ECO:0000269|PubMed:7545005"
FT MUTAGEN 100
FT /note="K->A: Reduced activity."
FT /evidence="ECO:0000269|PubMed:7545005"
FT MUTAGEN 103
FT /note="K->A,Q: Drastically reduced activity."
FT /evidence="ECO:0000269|PubMed:7545005"
FT MUTAGEN 124
FT /note="D->N: Loss of activity."
FT /evidence="ECO:0000269|PubMed:7545005"
FT MUTAGEN 125
FT /note="D->N: Loss of activity."
FT /evidence="ECO:0000269|PubMed:7545005"
FT HELIX 3..14
FT /evidence="ECO:0007829|PDB:1LH0"
FT STRAND 17..24
FT /evidence="ECO:0007829|PDB:1LH0"
FT STRAND 30..35
FT /evidence="ECO:0007829|PDB:1LH0"
FT HELIX 37..39
FT /evidence="ECO:0007829|PDB:1LH0"
FT HELIX 43..60
FT /evidence="ECO:0007829|PDB:1LH0"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:1LH0"
FT TURN 71..73
FT /evidence="ECO:0007829|PDB:1LH0"
FT HELIX 74..89
FT /evidence="ECO:0007829|PDB:1LH0"
FT STRAND 94..98
FT /evidence="ECO:0007829|PDB:1LH0"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:1OPR"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:1LH0"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:1LH0"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:1LH0"
FT HELIX 132..142
FT /evidence="ECO:0007829|PDB:1LH0"
FT STRAND 146..155
FT /evidence="ECO:0007829|PDB:1LH0"
FT STRAND 161..165
FT /evidence="ECO:0007829|PDB:1LH0"
FT HELIX 166..174
FT /evidence="ECO:0007829|PDB:1LH0"
FT STRAND 177..183
FT /evidence="ECO:0007829|PDB:1LH0"
FT HELIX 184..193
FT /evidence="ECO:0007829|PDB:1LH0"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:1LH0"
FT HELIX 198..211
FT /evidence="ECO:0007829|PDB:1LH0"
SQ SEQUENCE 213 AA; 23562 MW; 963A8BE3DD9113B0 CRC64;
MKPYQRQFIE FALNKQVLKF GEFTLKSGRK SPYFFNAGLF NTGRDLALLG RFYAEALVDS
GIEFDLLFGP AYKGIPIATT TAVALAEHHD KDLPYCFNRK EAKDHGEGGS LVGSALQGRV
MLVDDVITAG TAIRESMEII QAHGATLAGV LISLDRQERG RGEISAIQEV ERDYGCKVIS
IITLKDLIAY LEEKPDMAEH LAAVRAYREE FGV
