Dihydrofolate reductase - Lactobacillus casei

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Reviewed, UniProtKB/Swiss-Prot P00381 (DYR_LACCA)

Last modified November 25, 2008. Version 72. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein names

Recommended name:
Dihydrofolate reductase
EC=1.5.1.3

Gene names

Name:	folA
Synonyms:	dhfR

Organism

Lactobacillus casei

Taxonomic identifier

Taxonomic lineage

Bacteria › Firmicutes › Lactobacillales › Lactobacillaceae › Lactobacillus

Protein attributes

Sequence length	163 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
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.
Subunit structure	Monomer.
Miscellaneous	This bacterial strain is resistant to the folic acid analog methotrexate (amethopterin). 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
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	glycine biosynthetic process Inferred from electronic annotation. Source: InterPro nucleotide biosynthetic process Inferred from electronic annotation. Source: InterPro one-carbon compound metabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW response to antibiotic Inferred from electronic annotation. Source: UniProtKB-KW response to methotrexate Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	NADP binding Inferred from electronic annotation. Source: InterPro dihydrofolate reductase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

Removed

Chain

162

Dihydrofolate reductase

PRO_0000186393

Regions

Domain

160

DHFR

Nucleotide binding

21

NADP Potential

Sites

Binding site

1

Methotrexate

Binding site

1

Methotrexate

Binding site

1

Methotrexate

Site

1

May be important for enzyme function

Experimental info

Sequence conflict

1

D → N AA sequence Ref.2

Sequence conflict

1

P → L AA sequence Ref.2

Secondary structure

1

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163

Helix Strand Turn

Sequences

Sequence

Length

Mass (Da)

Tools

P00381-1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 1E4B556ED7A750D1
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163

18,439

        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

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: 3928445] [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: 98527] [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: 405008] [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: 6815179] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
[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: 1905571] [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: 7547901] [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: 9514736] [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: 10091649] [Abstract] Cited for: STRUCTURE BY NMR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

M10922 Genomic DNA. Translation: AAA25237.1.

PIR

RDLBD. A24036.

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AO8	NMR	-	A	1-163	[»]
1BZF	NMR	-	A	1-163	[»]
1DIS	NMR	-	A	1-163	[»]
1DIU	NMR	-	A	1-163	[»]
1LUD	NMR	-	A	1-163	[»]
2HM9	NMR	-	A	2-163	[»]
2HQP	NMR	-	A	2-163	[»]
3DFR	X-ray	1.70	A	1-163	[»]

ModBase

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]

ProtoNet

Other Resources

LinkHub

Entry information

Entry name

DYR_LACCA

Accession

Primary (citable) accession number: P00381

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	November 25, 2008
This is version 72 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

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

Relevant documents

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents