ID   DYRA_HALVD              Reviewed;         162 AA.
AC   P15093; D4GXA6; L9UT07;
DT   01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1990, sequence version 1.
DT   27-MAR-2024, entry version 130.
DE   RecName: Full=Dihydrofolate reductase HdrA;
DE            Short=DHFR A;
DE            Short=hDHFR-1;
DE            EC=1.5.1.3 {ECO:0000269|PubMed:2509470};
GN   Name=hdrA; Synonyms=folA; OrderedLocusNames=HVO_1279;
GN   ORFNames=C498_12348 {ECO:0000312|EMBL:ELY28035.1};
OS   Haloferax volcanii (strain ATCC 29605 / DSM 3757 / JCM 8879 / NBRC 14742 /
OS   NCIMB 2012 / VKM B-1768 / DS2) (Halobacterium volcanii).
OC   Archaea; Euryarchaeota; Stenosarchaea group; Halobacteria; Haloferacales;
OC   Haloferacaceae; Haloferax.
OX   NCBI_TaxID=309800;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-15, FUNCTION,
RP   CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RC   STRAIN=ATCC 29605 / DSM 3757 / JCM 8879 / NBRC 14742 / NCIMB 2012 /
RC   VKM B-1768 / DS2;
RX   PubMed=2509470; DOI=10.1016/s0021-9258(19)47238-4;
RA   Zusman T., Rosenshine I., Boehm G., Jaenicke R., Leskiw B., Mevarech M.;
RT   "Dihydrofolate reductase of the extremely halophilic archaebacterium
RT   Halobacterium volcanii. The enzyme and its coding gene.";
RL   J. Biol. Chem. 264:18878-18883(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 29605 / DSM 3757 / JCM 8879 / NBRC 14742 / NCIMB 2012 /
RC   VKM B-1768 / DS2;
RX   PubMed=20333302; DOI=10.1371/journal.pone.0009605;
RA   Hartman A.L., Norais C., Badger J.H., Delmas S., Haldenby S., Madupu R.,
RA   Robinson J., Khouri H., Ren Q., Lowe T.M., Maupin-Furlow J.,
RA   Pohlschroder M., Daniels C., Pfeiffer F., Allers T., Eisen J.A.;
RT   "The complete genome sequence of Haloferax volcanii DS2, a model
RT   archaeon.";
RL   PLoS ONE 5:E9605-E9605(2010).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 29605 / DSM 3757 / JCM 8879 / NBRC 14742 / NCIMB 2012 /
RC   VKM B-1768 / DS2;
RX   PubMed=25393412; DOI=10.1371/journal.pgen.1004784;
RA   Becker E.A., Seitzer P.M., Tritt A., Larsen D., Krusor M., Yao A.I., Wu D.,
RA   Madern D., Eisen J.A., Darling A.E., Facciotti M.T.;
RT   "Phylogenetically driven sequencing of extremely halophilic archaea reveals
RT   strategies for static and dynamic osmo-response.";
RL   PLoS Genet. 10:E1004784-E1004784(2014).
RN   [4] {ECO:0007744|PDB:1VDR}
RP   X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS).
RX   PubMed=9493269; DOI=10.1016/s0969-2126(98)00009-4;
RA   Pieper U., Kapadia G., Mevarech M., Herzberg O.;
RT   "Structural features of halophilicity derived from the crystal structure of
RT   dihydrofolate reductase from the Dead Sea halophilic archaeon, Haloferax
RT   volcanii.";
RL   Structure 6:75-88(1998).
RN   [5] {ECO:0007744|PDB:2ITH}
RP   STRUCTURE BY NMR.
RX   PubMed=17656587; DOI=10.1110/ps.072950407;
RA   Binbuga B., Boroujerdi A.F., Young J.K.;
RT   "Structure in an extreme environment: NMR at high salt.";
RL   Protein Sci. 16:1783-1787(2007).
RN   [6] {ECO:0007744|PDB:2JYB}
RP   STRUCTURE BY NMR.
RX   PubMed=18825778; DOI=10.1002/bip.21096;
RA   Boroujerdi A.F., Young J.K.;
RT   "NMR-derived folate-bound structure of dihydrofolate reductase 1 from the
RT   halophile Haloferax volcanii.";
RL   Biopolymers 91:140-144(2009).
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. {ECO:0000269|PubMed:2509470}.
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, ECO:0000269|PubMed:2509470};
CC   -!- ACTIVITY REGULATION: Activity unstable at KCl and NaCl concentrations
CC       lower than 2 M and activity increases with increasing concentrations of
CC       KCl or NaCl. {ECO:0000269|PubMed:2509470}.
CC   -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-
CC       tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
CC   -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; J05088; AAA72219.1; -; Genomic_DNA.
DR   EMBL; CP001956; ADE04659.1; -; Genomic_DNA.
DR   EMBL; AOHU01000091; ELY28035.1; -; Genomic_DNA.
DR   PIR; A34429; A34429.
DR   RefSeq; WP_004043660.1; NZ_AOHU01000091.1.
DR   PDB; 1VDR; X-ray; 2.55 A; A/B=1-162.
DR   PDB; 2ITH; NMR; -; A=1-162.
DR   PDB; 2JYB; NMR; -; A=1-162.
DR   PDBsum; 1VDR; -.
DR   PDBsum; 2ITH; -.
DR   PDBsum; 2JYB; -.
DR   AlphaFoldDB; P15093; -.
DR   BMRB; P15093; -.
DR   SMR; P15093; -.
DR   STRING; 309800.HVO_1279; -.
DR   PaxDb; 309800-C498_12348; -.
DR   EnsemblBacteria; ADE04659; ADE04659; HVO_1279.
DR   GeneID; 8925483; -.
DR   KEGG; hvo:HVO_1279; -.
DR   PATRIC; fig|309800.29.peg.2362; -.
DR   eggNOG; arCOG01490; Archaea.
DR   HOGENOM; CLU_043966_5_2_2; -.
DR   OrthoDB; 337010at2157; -.
DR   BRENDA; 1.5.1.3; 2561.
DR   UniPathway; UPA00077; UER00158.
DR   EvolutionaryTrace; P15093; -.
DR   Proteomes; UP000008243; Chromosome.
DR   Proteomes; UP000011532; Unassembled WGS sequence.
DR   GO; GO:0004146; F:dihydrofolate reductase activity; IEA:UniProtKB-EC.
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; IEA:UniProtKB-UniPathway.
DR   CDD; cd00209; DHFR; 1.
DR   Gene3D; 3.40.430.10; Dihydrofolate Reductase, subunit A; 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; DIHYDROFOLATE REDUCTASE; 1.
DR   PANTHER; PTHR48069:SF3; DIHYDROFOLATE REDUCTASE; 1.
DR   Pfam; PF00186; DHFR_1; 1.
DR   PIRSF; PIRSF000194; DHFR; 1.
DR   PRINTS; PR00070; DHFR.
DR   SUPFAM; SSF53597; Dihydrofolate reductase-like; 1.
DR   PROSITE; PS00075; DHFR_1; 1.
DR   PROSITE; PS51330; DHFR_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; NADP; One-carbon metabolism;
KW   Oxidoreductase; Reference proteome.
FT   CHAIN           1..162
FT                   /note="Dihydrofolate reductase HdrA"
FT                   /id="PRO_0000186433"
FT   DOMAIN          2..162
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:P0ABQ4"
FT   BINDING         14..20
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P0ABQ4"
FT   BINDING         29
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P0ABQ4"
FT   BINDING         47..48
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P0ABQ4"
FT   BINDING         67..68
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P0ABQ4"
FT   BINDING         101..108
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P0ABQ4"
FT   STRAND          3..11
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   STRAND          13..17
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   HELIX           27..36
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   STRAND          38..40
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   STRAND          42..45
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   HELIX           46..51
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   TURN            52..54
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   STRAND          58..64
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   STRAND          73..75
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   STRAND          78..81
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   HELIX           82..91
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   STRAND          97..101
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   HELIX           103..109
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   HELIX           110..112
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   STRAND          114..124
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   STRAND          128..130
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   TURN            136..138
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   STRAND          139..146
FT                   /evidence="ECO:0007829|PDB:1VDR"
FT   STRAND          151..157
FT                   /evidence="ECO:0007829|PDB:1VDR"
SQ   SEQUENCE   162 AA;  17980 MW;  31B047661F14281F CRC64;
     MELVSVAALA ENRVIGRDGE LPWPSIPADK KQYRSRIADD PVVLGRTTFE SMRDDLPGSA
     QIVMSRSERS FSVDTAHRAA SVEEAVDIAA SLDAETAYVI GGAAIYALFQ PHLDRMVLSR
     VPGEYEGDTY YPEWDAAEWE LDAETDHEGF TLQEWVRSAS SR
//