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Protein

Dihydrofolate reductase

Gene

dfrA

Organism
Bacillus anthracis
Status
Unreviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at protein leveli

Functioni

Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.UniRule annotation

Catalytic activityi

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.UniRule annotation

Pathway:itetrahydrofolate biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate.UniRule annotation
Proteins known to be involved in this subpathway in this organism are:
  1. Dihydrofolate reductase (dfrA)
This subpathway is part of the pathway tetrahydrofolate biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate, the pathway tetrahydrofolate biosynthesis and in Cofactor biosynthesis.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei8 – 81NADP; via amide nitrogen and carbonyl oxygenCombined sources
Binding sitei15 – 151NADP; via carbonyl oxygenCombined sources
Binding sitei79 – 791NADPCombined sources
Metal bindingi108 – 1081Calcium; via carbonyl oxygenCombined sources
Metal bindingi110 – 1101CalciumCombined sources
Metal bindingi147 – 1471CalciumCombined sources

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi19 – 202NADPCombined sources
Nucleotide bindingi45 – 473NADPCombined sources
Nucleotide bindingi63 – 653NADPCombined sources
Nucleotide bindingi98 – 1014NADPCombined sources

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

OxidoreductaseUniRule annotationImported

Keywords - Biological processi

One-carbon metabolismUniRule annotation

Keywords - Ligandi

CalciumCombined sources, Metal-bindingCombined sources, NADPCombined sources, Nucleotide-bindingCombined sources

Enzyme and pathway databases

BioCyciANTHRA:DFRA-MONOMER.
BANT260799:GJAJ-2151-MONOMER.
BANT261594:GJ7F-2226-MONOMER.
BRENDAi1.5.1.3. 634.
UniPathwayiUPA00077; UER00158.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydrofolate reductaseUniRule annotation (EC:1.5.1.3UniRule annotation)
Gene namesi
Name:dfrAImported
Synonyms:dfrDImported
Ordered Locus Names:GBAA_2237Imported
ORF Names:BF27_5333Imported
OrganismiBacillus anthracisImported
Taxonomic identifieri1392 [NCBI]
Taxonomic lineageiBacteriaFirmicutesBacilliBacillalesBacillaceaeBacillusBacillus cereus group
ProteomesiUP000000594 Componenti: Chromosome UP000031920 Componenti: Chromosome

Interactioni

Protein-protein interaction databases

STRINGi198094.BA_2237.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KGKNMR-A1-162[»]
2QK8X-ray2.40A1-162[»]
3DATX-ray2.30A1-162[»]
3E0BX-ray2.25A/B1-162[»]
3FL8X-ray2.29A/B/C/D/E/F/G/H1-162[»]
3FL9X-ray2.40A/B/C/D/E/F/G/H1-162[»]
3JVXX-ray2.25A/B1-162[»]
3JW3X-ray2.57A/B1-162[»]
3JW5X-ray2.89A/B1-162[»]
3JWCX-ray2.57A/B1-162[»]
3JWFX-ray2.57A/B1-162[»]
3JWKX-ray2.08A/B1-162[»]
3JWMX-ray2.57A/B1-162[»]
3S9UX-ray1.90A/B1-162[»]
3SA1X-ray2.50A/B1-162[»]
3SA2X-ray2.25A/B1-162[»]
3SAIX-ray2.25A/B1-162[»]
4ELBX-ray2.60A/B/C/D/E/F/G/H1-162[»]
4ELEX-ray2.35A/B/C/D/E/F/G/H1-162[»]
4ELFX-ray2.30A/B/C/D/E/F/G/H1-162[»]
4ELGX-ray2.10A/B/C/D/E/F/G/H1-162[»]
4ELHX-ray2.10A/B/C/D/E/F/G/H1-162[»]
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the dihydrofolate reductase family.UniRule annotation

Phylogenomic databases

KOiK00287.
OMAiIYLTHID.
OrthoDBiEOG6KT2V2.

Family and domain databases

Gene3Di3.40.430.10. 1 hit.
InterProiIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
[Graphical view]
PIRSFiPIRSF000194. DHFR. 1 hit.
PRINTSiPR00070. DHFR.
SUPFAMiSSF53597. SSF53597. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q81R22-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIVSFMVAMD ENRVIGKDNN LPWRLPSELQ YVKKTTMGHP LIMGRKNYEA
60 70 80 90 100
IGRPLPGRRN IIVTRNEGYH VEGCEVAHSV EEVFELCKNE EEIFIFGGAQ
110 120 130 140 150
IYDLFLPYVD KLYITKIHHA FEGDTFFPEM DMTNWKEVFV EKGLTDEKNP
160
YTYYYHVYEK QQ
Length:162
Mass (Da):19,125
Last modified:June 1, 2003 - v1
Checksum:i4259925DD9A1365A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AE017334 Genomic DNA. Translation: AAT31357.1.
AY569129 Genomic DNA. Translation: AAT40581.1.
CP009902 Genomic DNA. Translation: AJH87338.1.
RefSeqiWP_000637198.1. NZ_KN050651.1.

Genome annotation databases

EnsemblBacteriaiAAP26114; AAP26114; BA_2237.
AAT31357; AAT31357; GBAA_2237.
AAT54397; AAT54397; BAS2083.
AIF56465; AIF56465; HYU01_11160.
AIK08291; AIK08291; DH23_2166.
AIK33852; AIK33852; DJ48_2031.
AIK54032; AIK54032; DJ45_3684.
AIK57700; AIK57700; DJ44_442.
AJA86487; AJA86487; RT54_11060.
KFJ81276; KFJ81276; DJ42_799.
KFL65433; KFL65433; DJ49_2771.
KFL69605; KFL69605; DJ43_1447.
KGZ46380; KGZ46380; OY21_16995.
KGZ48612; KGZ48612; OY22_09325.
KGZ52451; KGZ52451; NX97_15125.
KGZ66505; KGZ66505; OY25_06805.
KGZ68589; KGZ68589; OY24_16705.
KGZ71566; KGZ71566; OY23_07725.
KGZ85346; KGZ85346; OY27_10805.
KGZ87656; KGZ87656; OY28_04730.
KGZ94037; KGZ94037; OY30_25630.
KGZ95202; KGZ95202; OY29_19330.
KGZ97845; KGZ97845; OY32_19775.
KHA13418; KHA13418; OY36_26740.
KHA14048; KHA14048; OY35_10095.
KHA14636; KHA14636; OY34_12150.
KHA23004; KHA23004; OY37_23510.
KHA23935; KHA23935; OY38_24710.
KHA40924; KHA40924; OY40_14725.
KHA42670; KHA42670; OY39_08650.
KHG44799; KHG44799; OY31_24910.
KHG51148; KHG51148; OY33_12840.
KHG61309; KHG61309; OY20_15790.
KEGGiban:BA_2237.
banh:HYU01_11160.
bar:GBAA_2237.
bat:BAS2083.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AE017334 Genomic DNA. Translation: AAT31357.1.
AY569129 Genomic DNA. Translation: AAT40581.1.
CP009902 Genomic DNA. Translation: AJH87338.1.
RefSeqiWP_000637198.1. NZ_KN050651.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KGKNMR-A1-162[»]
2QK8X-ray2.40A1-162[»]
3DATX-ray2.30A1-162[»]
3E0BX-ray2.25A/B1-162[»]
3FL8X-ray2.29A/B/C/D/E/F/G/H1-162[»]
3FL9X-ray2.40A/B/C/D/E/F/G/H1-162[»]
3JVXX-ray2.25A/B1-162[»]
3JW3X-ray2.57A/B1-162[»]
3JW5X-ray2.89A/B1-162[»]
3JWCX-ray2.57A/B1-162[»]
3JWFX-ray2.57A/B1-162[»]
3JWKX-ray2.08A/B1-162[»]
3JWMX-ray2.57A/B1-162[»]
3S9UX-ray1.90A/B1-162[»]
3SA1X-ray2.50A/B1-162[»]
3SA2X-ray2.25A/B1-162[»]
3SAIX-ray2.25A/B1-162[»]
4ELBX-ray2.60A/B/C/D/E/F/G/H1-162[»]
4ELEX-ray2.35A/B/C/D/E/F/G/H1-162[»]
4ELFX-ray2.30A/B/C/D/E/F/G/H1-162[»]
4ELGX-ray2.10A/B/C/D/E/F/G/H1-162[»]
4ELHX-ray2.10A/B/C/D/E/F/G/H1-162[»]
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi198094.BA_2237.

Chemistry

ChEMBLiCHEMBL5270.

Protocols and materials databases

DNASUi1085515.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAP26114; AAP26114; BA_2237.
AAT31357; AAT31357; GBAA_2237.
AAT54397; AAT54397; BAS2083.
AIF56465; AIF56465; HYU01_11160.
AIK08291; AIK08291; DH23_2166.
AIK33852; AIK33852; DJ48_2031.
AIK54032; AIK54032; DJ45_3684.
AIK57700; AIK57700; DJ44_442.
AJA86487; AJA86487; RT54_11060.
KFJ81276; KFJ81276; DJ42_799.
KFL65433; KFL65433; DJ49_2771.
KFL69605; KFL69605; DJ43_1447.
KGZ46380; KGZ46380; OY21_16995.
KGZ48612; KGZ48612; OY22_09325.
KGZ52451; KGZ52451; NX97_15125.
KGZ66505; KGZ66505; OY25_06805.
KGZ68589; KGZ68589; OY24_16705.
KGZ71566; KGZ71566; OY23_07725.
KGZ85346; KGZ85346; OY27_10805.
KGZ87656; KGZ87656; OY28_04730.
KGZ94037; KGZ94037; OY30_25630.
KGZ95202; KGZ95202; OY29_19330.
KGZ97845; KGZ97845; OY32_19775.
KHA13418; KHA13418; OY36_26740.
KHA14048; KHA14048; OY35_10095.
KHA14636; KHA14636; OY34_12150.
KHA23004; KHA23004; OY37_23510.
KHA23935; KHA23935; OY38_24710.
KHA40924; KHA40924; OY40_14725.
KHA42670; KHA42670; OY39_08650.
KHG44799; KHG44799; OY31_24910.
KHG51148; KHG51148; OY33_12840.
KHG61309; KHG61309; OY20_15790.
KEGGiban:BA_2237.
banh:HYU01_11160.
bar:GBAA_2237.
bat:BAS2083.

Phylogenomic databases

KOiK00287.
OMAiIYLTHID.
OrthoDBiEOG6KT2V2.

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.
BioCyciANTHRA:DFRA-MONOMER.
BANT260799:GJAJ-2151-MONOMER.
BANT261594:GJ7F-2226-MONOMER.
BRENDAi1.5.1.3. 634.

Family and domain databases

Gene3Di3.40.430.10. 1 hit.
InterProiIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
[Graphical view]
PIRSFiPIRSF000194. DHFR. 1 hit.
PRINTSiPR00070. DHFR.
SUPFAMiSSF53597. SSF53597. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Functional cloning of Bacillus anthracis dihydrofolate reductase and confirmation of natural resistance to trimethoprim."
    Barrow E.W., Bourne P.C., Barrow W.W.
    Antimicrob. Agents Chemother. 48:4643-4649(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE.
    Strain: SterneImported.
  2. "Crystal structure of the anthrax drug target, Bacillus anthracis dihydrofolate reductase."
    Bennett B.C., Xu H., Simmerman R.F., Lee R.E., Dealwis C.G.
    J. Med. Chem. 50:4374-4381(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS).
  3. "Synthetic and crystallographic studies of a new inhibitor series targeting Bacillus anthracis dihydrofolate reductase."
    Beierlein J.M., Frey K.M., Bolstad D.B., Pelphrey P.M., Joska T.M., Smith A.E., Priestley N.D., Wright D.L., Anderson A.C.
    J. Med. Chem. 51:7532-7540(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH NADP.
  4. "Crystal structure of Bacillus anthracis dihydrofolate reductase with the dihydrophthalazine-based trimethoprim derivative RAB1 provides a structural explanation of potency and selectivity."
    Bourne C.R., Bunce R.A., Bourne P.C., Berlin K.D., Barrow E.W., Barrow W.W.
    Antimicrob. Agents Chemother. 53:3065-3073(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.29 ANGSTROMS) IN COMPLEX WITH CALCIUM.
  5. "The solution structure of Bacillus anthracis dihydrofolate reductase yields insight into the analysis of structure-activity relationships for novel inhibitors."
    Beierlein J.M., Deshmukh L., Frey K.M., Vinogradova O., Anderson A.C.
    Biochemistry 48:4100-4108(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR IN COMPLEX WITH NADP.
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Ames ancestorImported and Ames AncestorImported.
  7. "X-ray structure of the ternary MTX.NADPH complex of the anthrax dihydrofolate reductase: a pharmacophore for dual-site inhibitor design."
    Bennett B.C., Wan Q., Ahmad M.F., Langan P., Dealwis C.G.
    J. Struct. Biol. 166:162-171(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH NADP.
  8. "Mutational Studies into Trimethoprim Resistance in Bacillus anthracis Dihydrofolate Reductase."
    Beierlein J.M., Karri N.G., Anderson A.C.
    Submitted (SEP-2009) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH NADP.
  9. "SAR studies of heterocyclic propargyl-linked TMP analogs targeting Bacillus dihydrofolate reductase."
    Anderson A.C., Beierlein J.M., Viswanathan K., Wright D.L.
    Submitted (JUN-2011) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH NADP.
  10. "SAR studies of heterocyclic propargyl-linked TMP analogs to Bacillus dihydrofolate reductase."
    Anderson A.C., Beierlein J.M., Viswanathan K., Wright D.L.
    Submitted (JUN-2011) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) IN COMPLEX WITH NADP.
  11. "Structure-Activity Studies of Heterocyclic Propargyl-linked TMP Analogs Targeting Bacillus anthracis Dihydrofolate Reductase."
    Anderson A.C., Beierlein J.M., Viswanathan K., Wright D.L.
    Submitted (JUN-2011) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH NADP.
  12. "Structure-activity relationship for enantiomers of potent inhibitors of B. anthracis dihydrofolate reductase."
    Bourne C.R., Wakeham N., Nammalwar B., Tseitin V., Bourne P.C., Barrow E.W., Mylvaganam S., Ramnarayan K., Bunce R.A., Berlin K.D., Barrow W.W.
    Biochim. Biophys. Acta 1834:46-52(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS).
  13. Cited for: NUCLEOTIDE SEQUENCE.
    Strain: 2002013094Imported.

Entry informationi

Entry nameiQ81R22_BACAN
AccessioniPrimary (citable) accession number: Q81R22
Secondary accession number(s): E9R6R2
, E9R6R3, E9R6R4, Q68SA0, Q6HZ92, Q6KT86
Entry historyi
Integrated into UniProtKB/TrEMBL: June 1, 2003
Last sequence update: June 1, 2003
Last modified: July 22, 2015
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusiUnreviewed (UniProtKB/TrEMBL)

Miscellaneousi

Keywords - Technical termi

3D-structureCombined sources, Complete proteome, Reference proteomeImported

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.