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P00381 (DYR_LACCA) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dihydrofolate reductase

EC=1.5.1.3
Gene names
Name:folA
Synonyms:dhfR
OrganismLactobacillus casei
Taxonomic identifier1582 [NCBI]
Taxonomic lineageBacteriaFirmicutesBacilliLactobacillalesLactobacillaceaeLactobacillus

Protein attributes

Sequence length163 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

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

Pathway

Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1.

Subunit structure

Monomer.

Miscellaneous

This bacterial strain is resistant to the folic acid analog methotrexate (amethopterin).

Sequence similarities

Belongs to the dihydrofolate reductase family.

Contains 1 DHFR (dihydrofolate reductase) domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.2 Ref.3
Chain2 – 163162Dihydrofolate reductase
PRO_0000186393

Regions

Domain2 – 161160DHFR
Nucleotide binding6 – 72NADP
Nucleotide binding14 – 196NADP
Nucleotide binding43 – 464NADP
Nucleotide binding63 – 664NADP
Nucleotide binding98 – 1036NADP
Region5 – 73Substrate binding

Sites

Binding site271Methotrexate
Binding site271Substrate
Binding site321Methotrexate
Binding site321Substrate
Binding site581Methotrexate
Binding site581Substrate
Binding site801NADP; via amide nitrogen
Binding site1171Substrate
Site221May be important for enzyme function

Experimental info

Sequence conflict91D → N AA sequence Ref.2
Sequence conflict911P → L AA sequence Ref.2

Secondary structure

...................................... 163
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P00381 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 1E4B556ED7A750D1

FASTA16318,439
        10         20         30         40         50         60 
MTAFLWAQDR DGLIGKDGHL PWHLPDDLHY FRAQTVGKIM VVGRRTYESF PKRPLPERTN 

        70         80         90        100        110        120 
VVLTHQEDYQ AQGAVVVHDV AAVFAYAKQH PDQELVIAGG AQIFTAFKDD VDTLLVTRLA 

       130        140        150        160 
GSFEGDTKMI PLNWDDFTKV SSRTVEDTNP ALTHTYEVWQ KKA 

« Hide

References

[1]"Nucleotide sequence of the dihydrofolate reductase gene of methotrexate-resistant Lactobacillus casei."
Andrews J., Clore G.M., Davies R.W., Gronenborn A.M., Gronenborn B., Kalderon D., Papadopoulos P.C., Schaefer S., Sims P.F.G., Stancombe R.
Gene 35:217-222(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Dihydrofolate reductase from amethopterin-resistant Lactobacillus casei. Sequences of the cyanogen bromide peptides and complete sequences of the enzyme."
Freisheim J.H., Bitar K.G., Reddy A.V., Blankenship D.T.
J. Biol. Chem. 253:6437-6444(1978) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-163.
[3]"Dihydrofolate reductase from Lactobacillus casei: N-terminal sequence and comparison with the substrate binding region of other reductases."
Batley K.E., Morris H.R.
Biochem. Biophys. Res. Commun. 75:1010-1014(1977) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-52.
[4]"Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7-A resolution. II. Environment of bound NADPH and implications for catalysis."
Filman D.J., Bolin J.T., Matthews D.A., Kraut J.
J. Biol. Chem. 257:13663-13672(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH NADPH AND METHOTREXATE.
[5]"Dihydrofolate reductase: sequential resonance assignments using 2D and 3D NMR and secondary structure determination in solution."
Carr M.D., Birdsall B., Frenkiel T.A., Bauer C.J., Jimenez-Barbero J., Polshakov V.I., McCormick J.E., Roberts G.C.K., Feeney J.
Biochemistry 30:6330-6341(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[6]"Solution structure of a brodimoprim analogue in its complex with Lactobacillus casei dihydrofolate reductase."
Morgan W.D., Birdsall B., Polshakov V.I., Sali D., Kompis I., Feeney J.
Biochemistry 34:11690-11702(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[7]"The solution structure of the complex of Lactobacillus casei dihydrofolate reductase with methotrexate."
Gargaro A.R., Soteriou A., Frenkiel T.A., Bauer C.J., Birdsall B., Polshakov V.I., Barsukov I.L., Roberts G.C.K., Feeney J.
J. Mol. Biol. 277:119-134(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[8]"Structure and dynamics in solution of the complex of Lactobacillus casei dihydrofolate reductase with the new lipophilic antifolate drug trimetrexate."
Polshakov V.I., Birdsall B., Frenkiel T.A., Gargaro A.R., Feeney J.
Protein Sci. 8:467-481(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M10922 Genomic DNA. Translation: AAA25237.1.
PIRRDLBD. A24036.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AO8NMR-A2-163[»]
1BZFNMR-A2-163[»]
1DISNMR-A2-163[»]
1DIUNMR-A2-163[»]
1LUDNMR-A2-163[»]
2HM9NMR-A2-163[»]
2HQPNMR-A2-163[»]
2L28NMR-A2-163[»]
2LF1NMR-A2-163[»]
3DFRX-ray1.70A2-163[»]
ProteinModelPortalP00381.
SMRP00381. Positions 2-163.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP00381.
ChEMBLCHEMBL2902.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Enzyme and pathway databases

SABIO-RKP00381.
UniPathwayUPA00077; UER00158.

Family and domain databases

Gene3D3.40.430.10. 1 hit.
InterProIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]
PfamPF00186. DHFR_1. 1 hit.
[Graphical view]
PIRSFPIRSF000194. DHFR. 1 hit.
PRINTSPR00070. DHFR.
SUPFAMSSF53597. SSF53597. 1 hit.
PROSITEPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP00381.

Entry information

Entry nameDYR_LACCA
AccessionPrimary (citable) accession number: P00381
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 101 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways