DYR_SCHMA
ID DYR_SCHMA Reviewed; 186 AA.
AC G4VJD6;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=Dihydrofolate reductase {ECO:0000303|PubMed:28288799};
DE EC=1.5.1.3 {ECO:0000269|PubMed:28288799};
GN Name=DHFR {ECO:0000303|PubMed:28288799};
GN ORFNames=Smp_175230 {ECO:0000312|EMBL:CCD79537.1};
OS Schistosoma mansoni (Blood fluke).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Platyhelminthes; Trematoda;
OC Digenea; Strigeidida; Schistosomatoidea; Schistosomatidae; Schistosoma.
OX NCBI_TaxID=6183;
RN [1] {ECO:0000312|EMBL:CCD79537.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Puerto Rican;
RA Protasio A.V., Tsai J.I., Babbage A., Nichol S., Hunt M., de Silva N.,
RA Anderson T.J.C., Clark R.C., Davidson C., Dillon G.P., Holroyd N.,
RA LoVerde P.T., Lloyd C., McQuillan J., Oliveira G., Otto T.D.,
RA Parker-Manuel S.J., Quail M.A., Wilson A., Zerlotini A., Dunne D.W.,
RA Berriman M.;
RT "A systematically improved high quality genome and transcriptome of the
RT human blood fluke Schistosoma mansoni.";
RL Submitted (OCT-2011) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0007744|PDB:3VCO}
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 1-181, FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND SUBUNIT.
RX PubMed=28288799; DOI=10.1016/j.actatropica.2017.03.007;
RA Serrao V.H.B., Romanello L., Cassago A., de Souza J.R.T., Cheleski J.,
RA DeMarco R., Brandao-Neto J., Pereira H.D.;
RT "Structure and kinetics assays of recombinant Schistosoma mansoni
RT dihydrofolate reductase.";
RL Acta Trop. 170:190-196(2017).
CC -!- FUNCTION: Key enzyme in folate metabolism. Contributes to the de novo
CC mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential
CC reaction for de novo glycine and purine synthesis, and for DNA
CC precursor synthesis. {ECO:0000269|PubMed:28288799}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
CC H(+) + NADPH; Xref=Rhea:RHEA:15009, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57451, ChEBI:CHEBI:57453, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.5.1.3;
CC Evidence={ECO:0000269|PubMed:28288799};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=26.4 uM for dihydrofolate {ECO:0000269|PubMed:28288799};
CC KM=123 uM for NADPH {ECO:0000269|PubMed:28288799};
CC Note=kcat is 35.9 sec(-1) for dihydrofolate. kcat is 130 sec(-1) for
CC NADPH. {ECO:0000269|PubMed:28288799};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-
CC tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
CC {ECO:0000269|PubMed:28288799}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:28288799}.
CC -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC {ECO:0000305}.
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DR EMBL; HE601627; CCD79537.1; -; Genomic_DNA.
DR RefSeq; XP_018652141.1; XM_018797062.1.
DR PDB; 3VCO; X-ray; 1.95 A; A=1-181.
DR PDBsum; 3VCO; -.
DR AlphaFoldDB; G4VJD6; -.
DR SMR; G4VJD6; -.
DR GeneID; 8344547; -.
DR KEGG; smm:Smp_175230; -.
DR CTD; 8344547; -.
DR eggNOG; KOG1324; Eukaryota.
DR HOGENOM; CLU_043966_2_3_1; -.
DR InParanoid; G4VJD6; -.
DR OMA; RDNQLPW; -.
DR OrthoDB; 1489621at2759; -.
DR PhylomeDB; G4VJD6; -.
DR BRENDA; 1.5.1.3; 5608.
DR UniPathway; UPA00077; UER00158.
DR Proteomes; UP000008854; Chromosome 4.
DR ExpressionAtlas; G4VJD6; baseline.
DR GO; GO:0004146; F:dihydrofolate reductase activity; IDA:UniProtKB.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0006545; P:glycine biosynthetic process; IEA:InterPro.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IDA:UniProtKB.
DR CDD; cd00209; DHFR; 1.
DR Gene3D; 3.40.430.10; -; 1.
DR InterPro; IPR012259; DHFR.
DR InterPro; IPR024072; DHFR-like_dom_sf.
DR InterPro; IPR017925; DHFR_CS.
DR InterPro; IPR001796; DHFR_dom.
DR PANTHER; PTHR48069; PTHR48069; 1.
DR Pfam; PF00186; DHFR_1; 1.
DR SUPFAM; SSF53597; SSF53597; 1.
DR PROSITE; PS00075; DHFR_1; 1.
DR PROSITE; PS51330; DHFR_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; NADP; One-carbon metabolism; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..186
FT /note="Dihydrofolate reductase"
FT /id="PRO_0000450383"
FT DOMAIN 2..180
FT /note="DHFR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT BINDING 8
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P00374"
FT BINDING 14..20
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P00374"
FT BINDING 28..33
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00374"
FT BINDING 51..53
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P00374"
FT BINDING 67
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00374"
FT BINDING 73..75
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P00374"
FT BINDING 112..119
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P00374"
FT STRAND 3..9
FT /evidence="ECO:0007829|PDB:3VCO"
FT TURN 22..24
FT /evidence="ECO:0007829|PDB:3VCO"
FT HELIX 26..37
FT /evidence="ECO:0007829|PDB:3VCO"
FT STRAND 44..50
FT /evidence="ECO:0007829|PDB:3VCO"
FT HELIX 51..56
FT /evidence="ECO:0007829|PDB:3VCO"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:3VCO"
FT STRAND 67..72
FT /evidence="ECO:0007829|PDB:3VCO"
FT STRAND 84..88
FT /evidence="ECO:0007829|PDB:3VCO"
FT HELIX 89..96
FT /evidence="ECO:0007829|PDB:3VCO"
FT TURN 99..104
FT /evidence="ECO:0007829|PDB:3VCO"
FT STRAND 105..110
FT /evidence="ECO:0007829|PDB:3VCO"
FT HELIX 114..122
FT /evidence="ECO:0007829|PDB:3VCO"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:3VCO"
FT STRAND 128..136
FT /evidence="ECO:0007829|PDB:3VCO"
FT HELIX 150..152
FT /evidence="ECO:0007829|PDB:3VCO"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:3VCO"
FT STRAND 171..180
FT /evidence="ECO:0007829|PDB:3VCO"
SQ SEQUENCE 186 AA; 21089 MW; 80859044A96924FD CRC64;
MRLNVVVAVS ENWGIGKGGG LPWKIKKDME FFKTVTTKAH PGLKNAVVMG RVTWESIPES
FKPLKDRINI VVSSTLSHAP SFVQVVPSLN AAIDLLYNEE FSSIVDEVFI IGGYRLYKEA
LKQSIYPVRI YCTHILSEVD CDTYFPKVDW DKLKKVDLPD IPADTFTENG FTFKFCVYDV
PSEQFI
