Reviewed, UniProtKB/Swiss-Prot P22906 (DYR_CANAL)

Names and origin

Protein names

Recommended name:
    Dihydrofolate reductase
    EC=1.5.1.3

Gene names

Name:

DFR1

Organism

Candida albicans (Yeast)

Taxonomic identifier

5476 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › mitosporic Saccharomycetales › Candida

Protein attributes

Sequence length	192 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
Sequence similarities	Belongs to the dihydrofolate reductase family. Contains 1 DHFR (dihydrofolate reductase) domain.

Ontologies

Keywords
Biological process	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 metabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	NADP or NADPH binding Inferred from electronic annotation. Source: InterPro dihydrofolate reductase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 192

192

Dihydrofolate reductase

PRO_0000186374

Regions

Domain

5 – 191

187

DHFR

Nucleotide binding

18 – 24

7

NADP

Nucleotide binding

56 – 58

3

NADP

Nucleotide binding

78 – 80

3

NADP

Nucleotide binding

113 – 120

8

NADP

Region

32 – 37

6

Substrate binding

Sites

Binding site

11

1

NADP; via amide nitrogen and carbonyl oxygen

Binding site

72

1

Substrate By similarity

Binding site

112

1

Substrate; via carbonyl oxygen

Binding site

118

1

Substrate

Natural variations

Natural variant

2

1

S → L in strain: SYNTEX CA755.

Natural variant

84

1

K → E in strain: SYNTEX CA755.

Secondary structure

1

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192

Helix Strand Turn

Details...

Beta strand

6 – 13

8

Turn

14 – 17

4

Beta strand

18 – 21

4

Helix

30 – 41

12

Beta strand

49 – 55

7

Helix

56 – 61

6

Helix

64 – 66

3

Beta strand

72 – 77

6

Beta strand

84 – 87

4

Beta strand

90 – 95

6

Helix

96 – 100

5

Beta strand

105 – 111

7

Helix

115 – 121

7

Beta strand

127 – 136

10

Beta strand

140 – 143

4

Helix

153 – 155

3

Beta strand

156 – 158

3

Helix

161 – 168

8

Beta strand

175 – 179

5

Beta strand

182 – 191

10

Sequences

	Sequence		Length	Mass (Da)
	P22906-1 [UniParc]. Last modified November 1, 1995. Version 4. Checksum: D8E3BEAC1DCADB4C	FASTA	192	22,139
	10 20 30 40 50 60 MSKPNVAIIV AALKPALGIG YKGKMPWRLR KEIRYFKDVT TRTTKPNTRN AVIMGRKTWE 70 80 90 100 110 120 SIPQKFRPLP DRLNIILSRS YENKIIDDNI IHASSIESSL NLVSDVERVF IIGGAEIYNE 130 140 150 160 170 180 LINNSLVSHL LITEIEHPSP ESIEMDTFLK FPLESWTKQP KSELQKFVGD TVLEDDIKEG 190 DFTYNYTLWT RK

References

[1]	"Sequence of a dihydrofolate reductase-encoding gene from Candida albicans." Daly S., Mastromei G., Yacoub A., Lorenzetti R. Gene 147:115-118(1994) [PubMed: 7916311] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 10127/5.
[2]	"Characterization of Candida albicans dihydrofolate reductase." Baccanari D.P., Tansik R.L., Joyner S.S., Fling M.E., Smith P.L., Freisheim J.H. J. Biol. Chem. 264:1100-1107(1989) [PubMed: 2642898] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-25, NUCLEOTIDE SEQUENCE OF 26-36.
[3]	"X-ray crystallographic studies of Candida albicans dihydrofolate reductase. High resolution structures of the holoenzyme and an inhibited ternary complex." Whitlow M., Howard A.J., Stewart D., Hardman K.D., Kuyper L.F., Baccanari D.P., Fling M.E., Tansik R.L. J. Biol. Chem. 272:30289-30298(1997) [PubMed: 9374515] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS). Strain: SYNTEX CA755.
[4]	"X-Ray crystal structures of Candida albicans dihydrofolate reductase: high resolution ternary complexes in which the dihydronicotinamide moiety of NADPH is displaced by an inhibitor." Whitlow M., Howard A.J., Stewart D., Hardman K.D., Chan J.H., Baccanari D.P., Tansik R.L., Hong J.S., Kuyper L.F. J. Med. Chem. 44:2928-2932(2001) [PubMed: 11520201] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH NADPH AND INHIBITOR.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X78968 Genomic DNA. Translation: CAA55561.1.
U84588 Genomic DNA. Translation: AAC05610.1.

PIR

A32203.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AI9	X-ray	1.85	A/B	3-192	[»]
1AOE	X-ray	1.60	A/B	3-192	[»]
1IA1	X-ray	1.70	A/B	3-192	[»]
1IA2	X-ray	1.82	A/B	3-192	[»]
1IA3	X-ray	1.78	A/B	3-192	[»]
1IA4	X-ray	1.85	A/B	3-192	[»]
1M78	X-ray	1.71	A/B	3-192	[»]
1M79	X-ray	1.70	A/B	3-192	[»]
1M7A	X-ray	1.76	A/B	3-192	[»]

ModBase

Search...

Enzyme and pathway databases

BRENDA

1.5.1.3. 1124.

Family and domain databases

InterPro

IPR012259. DHFR.
IPR017925. Dihydrofolate_reductase_CS.
IPR001796. Dihydrofolate_reductase_dom.
[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

Search...

Other Resources

BindingDB

P22906.

Entry information

Entry name

DYR_CANAL

Accession

Primary (citable) accession number: P22906
Secondary accession number(s): O59840

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	November 1, 1995
Last modified:	February 9, 2010
This is version 69 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

FPAP (Fungal Proteome Annotation Project)