Reviewed, UniProtKB/Swiss-Prot P0ABQ4 (DYR_ECOLI)

Names and origin

Protein names

Dihydrofolate reductase
Also known as:
     EC 1.5.1.3

Gene names

Name:	folA
Synonyms:	tmrA
Ordered Locus Names:	b0048, JW0047

Organism

Escherichia coli (strain K12) [Complete proteome] [HAMAP]

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia

Protein existence

Evidence at protein level.

General annotation (Comments)

Catalytic activity	5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH.
Pathway	Cofactor biosynthesis; tetrahydrofolate biosynthesis; tetrahydrofolate from dihydrofolate: step 1/1.
Miscellaneous	The strain K12 sequence is shown. Strain B [RT500] is resistant to 500 micrograms per milliliter of trimethoprim. Strain B [MB1428] is methotrexate-resistant. The reaction catalyzed by this enzyme represents an essential step for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP.
Sequence similarities	Belongs to the dihydrofolate reductase family. Contains 1 DHFR (dihydrofolate reductase) domain.

Ontologies

Keywords
Biological process	Antibiotic resistance Methotrexate resistance One-carbon metabolism Trimethoprim resistance
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
None. [Check GOA]

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 159

159

Dihydrofolate reductase

Regions

Domain

1 – 158

158

DHFR

Natural variations

Natural variant

28

1

L → R in strain: B[RT500] isozyme 2.

Natural variant

30

1

W → G in strain: 1810.

Natural variant

154

1

E → K in strain: B[MB1428].

Natural variant

154

1

E → Q in strain: 1810.

Secondary structure

1

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159

Helix Strand Turn

Details...

Beta strand

2 – 5

4

Helix

10 – 12

3

Helix

25 – 35

11

Beta strand

38 – 43

6

Helix

44 – 50

7

Beta strand

57 – 62

6

Beta strand

70 – 77

8

Helix

78 – 83

6

Beta strand

91 – 95

5

Helix

97 – 103

7

Helix

104 – 106

3

Beta strand

107 – 115

9

Beta strand

132 – 141

10

Beta strand

151 – 158

8

Sequences

	Sequence		Length	Mass (Da)
	P0ABQ4-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 6A03CDCD7F5F8562	FASTA	159	17,999
	10 20 30 40 50 60 MISLIAALAV DRVIGMENAM PWNLPADLAW FKRNTLNKPV IMGRHTWESI GRPLPGRKNI 70 80 90 100 110 120 ILSSQPGTDD RVTWVKSVDE AIAACGDVPE IMVIGGGRVY EQFLPKAQKL YLTHIDAEVE 130 140 150 GDTHFPDYEP DDWESVFSEF HDADAQNSHS YCFEILERR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The amino-acid sequence of the dihydrofolate reductase of a trimethoprim-resistant strain of Escherichia coli." Stone D., Phillips A.W., Burchall J.J. Eur. J. Biochem. 72:613-624(1977) [PubMed: 320005] [Abstract] Cited for: PROTEIN SEQUENCE (ISOZYME 1). Strain: B [RT500].
[2]	"Dihydrofolate reductase: the amino acid sequence of the enzyme from a methotrexate-resistant mutant of Escherichia coli." Bennett C.D., Rodkey J.A., Sondey J.M., Hirschmann R. Biochemistry 17:1328-1337(1978) [PubMed: 350268] [Abstract] Cited for: PROTEIN SEQUENCE. Strain: B [MB1428].
[3]	"Nucleotide sequence of the E coli gene coding for dihydrofolate reductase." Smith D.R., Calvo J.M. Nucleic Acids Res. 8:2255-2274(1980) [PubMed: 6159575] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12.
[4]	"Effect of a single amino acid substitution on Escherichia coli dihydrofolate reductase catalysis and ligand binding." Baccanari D.P., Stone D., Kuyper L. J. Biol. Chem. 256:1738-1747(1981) [PubMed: 7007370] [Abstract] Cited for: PROTEIN SEQUENCE (ISOZYME 2). Strain: B [RT500].
[5]	"Massive overproduction of dihydrofolate reductase in bacteria as a response to the use of trimethoprim." Flensburg J., Skoeld O. Eur. J. Biochem. 162:473-476(1987) [PubMed: 3549289] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 1810.
[6]	"Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region." Yura T., Mori H., Nagai H., Nagata T., Ishihama A., Fujita N., Isono K., Mizobuchi K., Nakata A. Nucleic Acids Res. 20:3305-3308(1992) [PubMed: 1630901] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12.
[7]	"The complete genome sequence of Escherichia coli K-12." Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y. Science 277:1453-1474(1997) [PubMed: 9278503] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[8]	"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T. Mol. Syst. Biol. 2:E1-E5(2006) [PubMed: 16738553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[9]	"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: 6815179] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
[10]	"Crystal structures of Escherichia coli dihydrofolate reductase: the NADP+ holoenzyme and the folate.NADP+ ternary complex. Substrate binding and a model for the transition state." Bystroff C., Oatley S.J., Kraut J. Biochemistry 29:3263-3277(1990) [PubMed: 2185835] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
[11]	"Crystal structure of unliganded Escherichia coli dihydrofolate reductase. Ligand-induced conformational changes and cooperativity in binding." Bystroff C., Kraut J. Biochemistry 30:2227-2239(1991) [PubMed: 1998681] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).

Cross-references

Sequence databases

EMBLGenBankDDBJ

J01609 Genomic DNA. Translation: AAA87976.1.
X05108 Genomic DNA. Translation: CAA28755.1.
U00096 Genomic DNA. Translation: AAC73159.1.
AP009048 Genomic DNA. Translation: BAB96616.1.

PIR

RDECD. A93704.

RefSeq

AP_000712.1.
NP_414590.1.

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DDR	X-ray	2.45	A/B	1-159	[»]
1DDS	X-ray	2.20	A/B	1-159	[»]
1DHI	X-ray	1.90	A/B	1-159	[»]
1DHJ	X-ray	1.80	A/B	1-159	[»]
1DRA	X-ray	1.90	A/B	1-159	[»]
1DRB	X-ray	1.96	A/B	1-159	[»]
1DRE	X-ray	2.60	A	1-159	[»]
1DRH	X-ray	2.30	A	1-159	[»]
1DYH	X-ray	1.90	A/B	1-159	[»]
1DYI	X-ray	1.90	A/B	1-159	[»]
1DYJ	X-ray	1.85	A/B	1-159	[»]
1JOL	X-ray	1.96	A/B	1-159	[»]
1JOM	X-ray	1.90	A	1-159	[»]
1RA1	X-ray	1.90	A	1-159	[»]
1RA2	X-ray	1.60	A	1-159	[»]
1RA3	X-ray	1.80	A	1-159	[»]
1RA8	X-ray	1.80	A	1-159	[»]
1RA9	X-ray	1.55	A	1-159	[»]
1RB2	X-ray	2.10	A/B	1-159	[»]
1RB3	X-ray	2.30	A/B	1-159	[»]
1RC4	X-ray	1.90	A	1-159	[»]
1RD7	X-ray	2.60	A/B	1-159	[»]
1RE7	X-ray	2.60	A/B	1-159	[»]
1RF7	X-ray	1.80	A	1-159	[»]
1RG7	X-ray	2.00	A	1-159	[»]
1RH3	X-ray	2.40	A	1-159	[»]
1RX1	X-ray	2.00	A	1-159	[»]
1RX2	X-ray	1.80	A	1-159	[»]
1RX3	X-ray	2.20	A	1-159	[»]
1RX4	X-ray	2.20	A	1-159	[»]
1RX5	X-ray	2.30	A	1-159	[»]
1RX6	X-ray	2.00	A	1-159	[»]
1RX7	X-ray	2.30	A	1-159	[»]
1RX8	X-ray	2.80	A	1-159	[»]
1RX9	X-ray	1.90	A	1-159	[»]
1TDR	X-ray	2.50	A/B	1-159	[»]
2ANO	X-ray	2.68	A	1-159	[»]
2ANQ	X-ray	2.13	A	1-159	[»]
2D0K	X-ray	1.90	A/B	1-159	[»]
2DRC	X-ray	1.90	A/B	1-159	[»]
2INQ	neutron diffraction	2.20	A/B	1-159	[»]
3DRC	X-ray	1.90	A/B	1-159	[»]
4DFR	X-ray	1.70	A/B	1-159	[»]
5DFR	X-ray	2.30	A	1-159	[»]
6DFR	X-ray	2.40	A	1-159	[»]
7DFR	X-ray	2.50	A	1-159	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P0ABQ4.

2-D gel databases

SWISS-2DPAGE

P0ABQ4.

ECO2DBASE

B020.0. 6TH EDITION.

Genome annotation databases

GeneID

944790.

GenomeReviews

Gene locus b0048 in contig U00096_GR.
Gene locus JW0047 in contig AP009048_GR.

KEGG

ecj:JW0047.
eco:b0048.

Organism-specific databases

EchoBASE

EB0322.

EcoGene

EG10326. folA.

CMR

Search...

Phylogenomic databases

HOGENOM

P0ABQ4.

Enzyme and pathway databases

BioCyc

EcoCyc:DIHYDROFOLATEREDUCT-MON.

Family and domain databases

InterPro

IPR012259. DHFR.
IPR001796. DHFR_reg.
[Graphical view]

PANTHER

PTHR11549:SF1. DHFR. 1 hit.

Pfam

PF00186. DHFR_1. 1 hit.
[Graphical view]

PRINTS

PR00070. DHFR.

PROSITE

PS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]

ProDom

P0ABQ4.
[Graphical view] [Entries sharing at least one domain]

BLOCKS

Search...

Other Resources

LinkHub

P0ABQ4.

ProtoNet

Search...

Entry information

Entry name

DYR_ECOLI

Accession

Primary (citable) accession number: P0ABQ4
Secondary accession number(s): P00379

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	June 10, 2008
This is version 32 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HAMAP (High-quality Automated and Manual Annotation of microbial Proteomes)