DYR_THEMA
ID DYR_THEMA Reviewed; 169 AA.
AC Q60034; P96109;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Dihydrofolate reductase;
DE Short=DHFR;
DE EC=1.5.1.3;
GN Name=folA; Synonyms=dyrA; OrderedLocusNames=TM_1641;
OS Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826
OS / MSB8).
OC Bacteria; Thermotogae; Thermotogales; Thermotogaceae; Thermotoga.
OX NCBI_TaxID=243274;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7789791; DOI=10.1016/0378-1119(95)00090-s;
RA van de Casteele M., Legrain C., Wilquet V., Glansdorff N.;
RT "The dihydrofolate reductase-encoding gene dyrA of the hyperthermophilic
RT bacterium Thermotoga maritima.";
RL Gene 158:101-105(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8;
RX PubMed=9563834;
RA Dams T., Schurig H., Jaenicke R.;
RT "Homo-dimeric recombinant dihydrofolate reductase from Thermotoga maritima
RT shows extreme intrinsic stability.";
RL Biol. Chem. 379:367-371(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8;
RX PubMed=10360571; DOI=10.1038/20601;
RA Nelson K.E., Clayton R.A., Gill S.R., Gwinn M.L., Dodson R.J., Haft D.H.,
RA Hickey E.K., Peterson J.D., Nelson W.C., Ketchum K.A., McDonald L.A.,
RA Utterback T.R., Malek J.A., Linher K.D., Garrett M.M., Stewart A.M.,
RA Cotton M.D., Pratt M.S., Phillips C.A., Richardson D.L., Heidelberg J.F.,
RA Sutton G.G., Fleischmann R.D., Eisen J.A., White O., Salzberg S.L.,
RA Smith H.O., Venter J.C., Fraser C.M.;
RT "Evidence for lateral gene transfer between Archaea and Bacteria from
RT genome sequence of Thermotoga maritima.";
RL Nature 399:323-329(1999).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH METHOTREXATE AND
RP NADPH.
RX PubMed=10731419; DOI=10.1006/jmbi.2000.3570;
RA Dams T., Auerbach G., Bader G., Jacob U., Ploom T., Huber R., Jaenicke R.;
RT "The crystal structure of dihydrofolate reductase from Thermotoga maritima:
RT molecular features of thermostability.";
RL J. Mol. Biol. 297:659-672(2000).
CC -!- FUNCTION: Key enzyme in folate metabolism. Catalyzes an essential
CC reaction for de novo glycine and purine synthesis, and for DNA
CC precursor synthesis (By similarity). {ECO:0000250}.
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; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00660};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Temperature dependence:
CC Highly thermostable.;
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-
CC tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10731419}.
CC -!- INTERACTION:
CC Q60034; Q60034: folA; NbExp=2; IntAct=EBI-25642550, EBI-25642550;
CC -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD36708.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; X81845; CAA57437.1; -; Genomic_DNA.
DR EMBL; Y11021; CAA71903.1; -; Genomic_DNA.
DR EMBL; AE000512; AAD36708.1; ALT_INIT; Genomic_DNA.
DR PIR; A72231; A72231.
DR RefSeq; NP_229441.1; NC_000853.1.
DR RefSeq; WP_004082129.1; NZ_CP011107.1.
DR PDB; 1CZ3; X-ray; 2.10 A; A/B=2-169.
DR PDB; 1D1G; X-ray; 2.10 A; A/B=2-169.
DR PDBsum; 1CZ3; -.
DR PDBsum; 1D1G; -.
DR AlphaFoldDB; Q60034; -.
DR SMR; Q60034; -.
DR STRING; 243274.THEMA_06040; -.
DR EnsemblBacteria; AAD36708; AAD36708; TM_1641.
DR KEGG; tma:TM1641; -.
DR PATRIC; fig|243274.5.peg.1660; -.
DR eggNOG; COG0262; Bacteria.
DR InParanoid; Q60034; -.
DR OMA; IMVQSIN; -.
DR BioCyc; MetaCyc:MON-461; -.
DR BRENDA; 1.5.1.3; 6331.
DR UniPathway; UPA00077; UER00158.
DR EvolutionaryTrace; Q60034; -.
DR Proteomes; UP000008183; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0004146; F:dihydrofolate reductase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0050661; F:NADP binding; IBA:GO_Central.
DR GO; GO:0046452; P:dihydrofolate metabolic process; IBA:GO_Central.
DR GO; GO:0046655; P:folic acid metabolic process; IBA:GO_Central.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IBA:GO_Central.
DR CDD; cd00209; DHFR; 1.
DR Gene3D; 3.40.430.10; -; 1.
DR InterPro; IPR024072; DHFR-like_dom_sf.
DR InterPro; IPR001796; DHFR_dom.
DR Pfam; PF00186; DHFR_1; 1.
DR SUPFAM; SSF53597; SSF53597; 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..169
FT /note="Dihydrofolate reductase"
FT /id="PRO_0000186418"
FT DOMAIN 3..169
FT /note="DHFR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT BINDING 7..8
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:10731419"
FT BINDING 9
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10731419"
FT BINDING 16
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10731419"
FT BINDING 28..30
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:10731419"
FT BINDING 46..51
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10731419"
FT BINDING 54
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:10731419"
FT BINDING 59
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:10731419"
FT BINDING 65..67
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10731419"
FT BINDING 81
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10731419"
FT BINDING 101
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:10731419"
FT BINDING 103..105
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10731419"
FT CONFLICT 68..81
FT /note="PKTSNNPSLVFFNG -> TQNFQQSFTRFFQR (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 108
FT /note="T -> S (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 138..139
FT /note="FE -> LQ (in Ref. 1)"
FT /evidence="ECO:0000305"
FT STRAND 3..10
FT /evidence="ECO:0007829|PDB:1CZ3"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:1CZ3"
FT HELIX 26..39
FT /evidence="ECO:0007829|PDB:1CZ3"
FT STRAND 41..45
FT /evidence="ECO:0007829|PDB:1CZ3"
FT HELIX 46..52
FT /evidence="ECO:0007829|PDB:1CZ3"
FT STRAND 59..64
FT /evidence="ECO:0007829|PDB:1CZ3"
FT STRAND 76..79
FT /evidence="ECO:0007829|PDB:1CZ3"
FT HELIX 83..92
FT /evidence="ECO:0007829|PDB:1CZ3"
FT STRAND 96..102
FT /evidence="ECO:0007829|PDB:1CZ3"
FT HELIX 104..112
FT /evidence="ECO:0007829|PDB:1CZ3"
FT STRAND 117..123
FT /evidence="ECO:0007829|PDB:1CZ3"
FT STRAND 125..130
FT /evidence="ECO:0007829|PDB:1CZ3"
FT STRAND 132..135
FT /evidence="ECO:0007829|PDB:1CZ3"
FT STRAND 141..151
FT /evidence="ECO:0007829|PDB:1CZ3"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:1CZ3"
FT STRAND 158..164
FT /evidence="ECO:0007829|PDB:1CZ3"
SQ SEQUENCE 169 AA; 19367 MW; F5DA22C978E2C39D CRC64;
MAKVIFVLAM DVSGKIASSV ESWSSFEDRK NFRKITTEIG NVVMGRITFE EIGRPLPERL
NVVLTRRPKT SNNPSLVFFN GSPADVVKFL EGKGYERVAV IGGKTVFTEF LREKLVDELF
VTVEPYVFGK GIPFFDEFEG YFPLKLLEMR RLNERGTLFL KYSVEKSHR
