P16184 (DYR_PNECA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Dihydrofolate reductase EC=1.5.1.3
Organism	Pneumocystis carinii
Taxonomic identifier	4754 [NCBI]
Taxonomic lineage	Eukaryota › Fungi › Dikarya › Ascomycota › Taphrinomycotina › Pneumocystidomycetes › Pneumocystidaceae › Pneumocystis

Protein attributes

Sequence length	206 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
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

Chain

1 – 206

206

Dihydrofolate reductase

PRO_0000186376

Regions

Domain

6 – 204

199

DHFR

Nucleotide binding

18 – 24

7

NADP

Nucleotide binding

59 – 61

3

NADP

Nucleotide binding

81 – 83

3

NADP

Nucleotide binding

124 – 131

8

NADP

Region

32 – 37

6

Substrate binding

Sites

Binding site

12

1

NADP; via amide nitrogen and carbonyl oxygen

Binding site

75

1

Substrate

Secondary structure

1

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206

Helix Strand Turn

Details...

Beta strand

7 – 14

8

Beta strand

18 – 21

4

Helix

30 – 41

12

Turn

45 – 50

6

Beta strand

52 – 58

7

Helix

59 – 63

5

Helix

67 – 69

3

Beta strand

75 – 80

6

Beta strand

93 – 97

5

Helix

98 – 108

11

Beta strand

117 – 122

6

Helix

126 – 133

8

Beta strand

138 – 146

9

Beta strand

153 – 155

3

Helix

163 – 165

3

Turn

166 – 168

3

Helix

174 – 181

8

Beta strand

190 – 192

3

Beta strand

195 – 203

9

Sequences

	Sequence		Length	Mass (Da)
	P16184 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: 6BA64A7019911508	FASTA	206	23,884
	10 20 30 40 50 60 MNQQKSLTLI VALTTSYGIG RSNSLPWKLK KEISYFKRVT SFVPTFDSFE SMNVVLMGRK 70 80 90 100 110 120 TWESIPLQFR PLKGRINVVI TRNESLDLGN GIHSAKSLDH ALELLYRTYG SESSVQINRI 130 140 150 160 170 180 FVIGGAQLYK AAMDHPKLDR IMATIIYKDI HCDVFFPLKF RDKEWSSVWK KEKHSDLESW 190 200 VGTKVPHGKI NEDGFDYEFE MWTRDL

References

[1]	"Isolation and expression of the Pneumocystis carinii dihydrofolate reductase gene." Edman J.C., Edman U., Cao M., Lundgren B., Kovacs J., Santi D.V. Proc. Natl. Acad. Sci. U.S.A. 86:8625-8629(1989) [PubMed: 2682653] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	"The structure of Pneumocystis carinii dihydrofolate reductase to 1.9-A resolution." Champness J.N., Achari A., Ballantine S.P., Bryant P.K., Delves C.J., Stammers D.K. Structure 2:915-924(1994) [PubMed: 7866743] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS).
[3]	"Ligand-induced conformational changes in the crystal structures of Pneumocystis carinii dihydrofolate reductase complexes with folate and NADP+." Cody V., Galitsky N., Rak D., Luft J.R., Pangborn W., Queener S.F. Biochemistry 38:4303-4312(1999) [PubMed: 10194348] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH FOLATE AND NADP.
[4]	"Structural studies on bioactive compounds. 30. Crystal structure and molecular modeling studies on the Pneumocystis carinii dihydrofolate reductase cofactor complex with TAB, a highly selective antifolate." Cody V., Chan D., Galitsky N., Rak D., Luft J.R., Pangborn W., Queener S.F., Laughton C.A., Stevens M.F. Biochemistry 39:3556-3564(2000) [PubMed: 10736154] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH NADP AND THE SYNTHETIC INHIBITOR TAB.
[5]	"Structure-based enzyme inhibitor design: modeling studies and crystal structure analysis of Pneumocystis carinii dihydrofolate reductase ternary complex with PT653 and NADPH." Cody V., Galitsky N., Luft J.R., Pangborn W., Rosowsky A., Queener S.F. Acta Crystallogr. D 58:946-954(2002) [PubMed: 12037296] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH PT653 AND NADPH.
[6]	"Analysis of quinazoline and pyrido[2,3-d]pyrimidine N9-C10 reversed-bridge antifolates in complex with NADP+ and Pneumocystis carinii dihydrofolate reductase." Cody V., Galitsky N., Luft J.R., Pangborn W., Queener S.F., Gangjee A. Acta Crystallogr. D 58:1393-1399(2002) [PubMed: 12198294] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITOR AND NADPH.
[7]	"Structure determination of tetrahydroquinazoline antifolates in complex with human and Pneumocystis carinii dihydrofolate reductase: correlations between enzyme selectivity and stereochemistry." Cody V., Luft J.R., Pangborn W., Gangjee A., Queener S.F. Acta Crystallogr. D 60:646-655(2004) [PubMed: 15039552] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR.
[8]	"New insights into DHFR interactions: analysis of Pneumocystis carinii and mouse DHFR complexes with NADPH and two highly potent 5-(omega-carboxy(alkyloxy) trimethoprim derivatives reveals conformational correlations with activity and novel parallel ring stacking interactions." Cody V., Pace J., Chisum K., Rosowsky A. Proteins 65:959-969(2006) [PubMed: 17019704] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH INHIBITOR AND NADPH.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M26495 Genomic DNA. Translation: AAA33787.1.
M26496 mRNA. Translation: AAA33788.1.

PIR

A36177.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CD2	X-ray	2.20	A	1-206	[»]
1DAJ	X-ray	2.30	A	1-206	[»]
1DYR	X-ray	1.86	A	1-206	[»]
1E26	X-ray	2.00	A	1-206	[»]
1KLK	X-ray	2.30	A	1-206	[»]
1LY3	X-ray	1.90	A	1-206	[»]
1LY4	X-ray	2.10	A	1-206	[»]
1S3Y	X-ray	2.25	A	1-206	[»]
1VJ3	X-ray	2.10	A	2-206	[»]
2CD2	X-ray	1.90	A	1-206	[»]
2FZH	X-ray	2.10	A	1-206	[»]
2FZI	X-ray	1.60	A	1-206	[»]
3CD2	X-ray	2.50	A	1-206	[»]
3NZ6	X-ray	2.00	X	1-206	[»]
3NZ9	X-ray	1.80	X	1-206	[»]
3NZA	X-ray	1.90	X	1-206	[»]
3NZB	X-ray	1.45	X	1-206	[»]
3NZC	X-ray	2.00	X	1-206	[»]
4CD2	X-ray	2.00	A	1-206	[»]

ProteinModelPortal

P16184.

SMR

P16184. Positions 1-206.

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]

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

P16184.

Entry information

Entry name

DYR_PNECA

Accession

Primary (citable) accession number: P16184

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	July 27, 2011
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program