P0A017 (DYR_STAAU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dihydrofolate reductase
Short name=DHFR
EC=1.5.1.3

Gene names

Name:

folA

Organism

Staphylococcus aureus

Taxonomic identifier

1280 [NCBI]

Taxonomic lineage

Bacteria › Firmicutes › Bacillales › Staphylococcus

Protein attributes

Sequence length	159 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)

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.
Miscellaneous	There are two dhfR isozymes in S.aureus, this one is chromosomal and is sensitive to trimethoprim.
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
Molecular function	NADP 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

Initiator methionine

1

1

Removed Ref.2

Chain

2 – 159

158

Dihydrofolate reductase

PRO_0000186411

Regions

Domain

2 – 157

156

DHFR

Nucleotide binding

7 – 8

2

NADP

Nucleotide binding

15 – 20

6

NADP

Nucleotide binding

44 – 47

4

NADP

Nucleotide binding

63 – 66

4

NADP

Nucleotide binding

93 – 98

6

NADP

Region

6 – 8

3

Substrate binding

Sites

Binding site

28

1

Substrate

Binding site

58

1

Substrate

Binding site

101

1

NADP

Binding site

112

1

Substrate

Binding site

122

1

NADP

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

159

Helix Strand Turn

Details...

Beta strand

3 – 10

8

Helix

26 – 36

11

Beta strand

40 – 43

4

Helix

46 – 50

5

Beta strand

58 – 63

6

Beta strand

75 – 77

3

Helix

80 – 85

6

Beta strand

90 – 92

3

Helix

97 – 102

6

Turn

103 – 105

3

Beta strand

107 – 114

8

Turn

129 – 131

3

Beta strand

132 – 138

7

Beta strand

150 – 157

8

Sequences

	Sequence		Length	Mass (Da)
	P0A017 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 811898409FEAFAAB	FASTA	159	18,251
	10 20 30 40 50 60 MTLSILVAHD LQRVIGFENQ LPWHLPNDLK HVKKLSTGHT LVMGRKTFES IGKPLPNRRN 70 80 90 100 110 120 VVLTSDTSFN VEGVDVIHSI EDIYQLPGHV FIFGGQTLFE EMIDKVDDMY ITVIEGKFRG 130 140 150 DTFFPPYTFE DWEVASSVEG KLDEKNTIPH TFLHLIRKK

References

[1]	"Characterization of the gene for chromosomal trimethoprim-sensitive dihydrofolate reductase of Staphylococcus aureus ATCC 25923." Dale G.E., Then R.L., Stueber D. Antimicrob. Agents Chemother. 37:1400-1405(1993) [PubMed: 8363365] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 25923 / DSM 1104 / Seattle 1945 / FO 14462 / JCM 2413.
[2]	"N-terminal amino acid sequence of the chromosomal dihydrofolate reductase purified from trimethoprim-resistant Staphylococcus aureus." Hartman P.G., Stahli M., Kocher H.P., Then R.L. FEBS Lett. 242:157-160(1988) [PubMed: 3060373] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-36. Strain: 157/4696.
[3]	"Inhibitory properties and X-ray crystallographic study of the binding of AR-101, AR-102 and iclaprim in ternary complexes with NADPH and dihydrofolate reductase from Staphylococcus aureus." Oefner C., Parisi S., Schulz H., Lociuro S., Dale G.E. Acta Crystallogr. D 65:751-757(2009) [PubMed: 19622858] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 2-159.
[4]	"Structural comparison of chromosomal and exogenous dihydrofolate reductase from Staphylococcus aureus in complex with the potent inhibitor trimethoprim." Heaslet H., Harris M., Fahnoe K., Sarver R., Putz H., Chang J., Subramanyam C., Barreiro G., Miller J.R. Proteins 76:706-717(2009) [PubMed: 19280600] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) IN COMPLEX WITH NADPH AND TRIMETHOPRIM.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z16422 Genomic DNA. Translation: CAA78910.1.

PIR

S32014.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2W9G	X-ray	1.95	A	1-159	[»]
2W9H	X-ray	1.48	A	1-159	[»]
3FRA	X-ray	2.35	X	2-159	[»]
3FRB	X-ray	2.00	X	2-159	[»]
3FRD	X-ray	2.10	X	2-159	[»]
3FRE	X-ray	2.20	X	2-159	[»]
3FRF	X-ray	2.20	X	2-159	[»]
3FY8	X-ray	2.20	X	2-159	[»]
3FY9	X-ray	2.25	X	2-159	[»]
3FYV	X-ray	2.20	X	2-159	[»]
3FYW	X-ray	2.10	X	2-159	[»]
3I8A	X-ray	2.41	X	2-158	[»]
3LG4	X-ray	3.15	A/B	1-158	[»]
3M08	X-ray	2.01	A	2-158	[»]
3M09	X-ray	2.01	A	2-158	[»]
3SQY	X-ray	1.50	X	1-159	[»]
3SR5	X-ray	1.68	X	2-159	[»]
3SRQ	X-ray	1.69	X	1-159	[»]
3SRR	X-ray	1.70	X	1-159	[»]
3SRS	X-ray	1.70	X	1-159	[»]
3SRU	X-ray	1.70	X	1-159	[»]
3SRW	X-ray	1.70	X	1-159	[»]

ProteinModelPortal

P0A017.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

IPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]

Gene3D

G3DSA:3.40.430.10. G3DSA:3.40.430.10. 1 hit.

PANTHER

PTHR11549:SF1. DHFR. 1 hit.

Pfam

PF00186. DHFR_1. 1 hit.
[Graphical view]

PIRSF

PIRSF000194. DHFR. 1 hit.

PRINTS

PR00070. DHFR.

SUPFAM

SSF53597. SSF53597. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

BindingDB

P0A017.

Entry information

Entry name

DYR_STAAU

Accession

Primary (citable) accession number: P0A017
Secondary accession number(s): P10167

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2005
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 45 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program