DYRA_HALVD
ID DYRA_HALVD Reviewed; 162 AA.
AC P15093; D4GXA6;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Dihydrofolate reductase HdrA;
DE Short=DHFR A;
DE Short=hDHFR-1;
DE EC=1.5.1.3;
GN Name=hdrA; Synonyms=folA; OrderedLocusNames=HVO_1279;
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 / VKM
RC 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 / VKM
RC 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 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 [4]
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 [5]
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 PIR; A34429; A34429.
DR RefSeq; WP_004043660.1; NC_013967.1.
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.C498_12348; -.
DR EnsemblBacteria; ADE04659; ADE04659; HVO_1279.
DR GeneID; 8925483; -.
DR KEGG; hvo:HVO_1279; -.
DR eggNOG; arCOG01490; Archaea.
DR HOGENOM; CLU_043966_5_2_2; -.
DR OMA; EECFVIG; -.
DR OrthoDB; 90233at2157; -.
DR BRENDA; 1.5.1.3; 2561.
DR UniPathway; UPA00077; UER00158.
DR EvolutionaryTrace; P15093; -.
DR Proteomes; UP000008243; Chromosome.
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; -; 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 PIRSF; PIRSF000194; DHFR; 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; 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"
FT BINDING 14..20
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 29
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 47..48
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 67..68
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 101..108
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
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
