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P16184 (DYR_PNECA) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dihydrofolate reductase

EC=1.5.1.3
OrganismPneumocystis carinii
Taxonomic identifier4754 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaTaphrinomycotinaPneumocystidomycetesPneumocystidaceaePneumocystis

Protein attributes

Sequence length206 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 206206Dihydrofolate reductase
PRO_0000186376

Regions

Domain6 – 204199DHFR
Nucleotide binding18 – 247NADP
Nucleotide binding59 – 613NADP
Nucleotide binding81 – 833NADP
Nucleotide binding124 – 1318NADP
Region32 – 376Substrate binding

Sites

Binding site121NADP; via amide nitrogen and carbonyl oxygen
Binding site751Substrate

Secondary structure

......................................... 206
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P16184 [UniParc].

Last modified April 1, 1990. Version 1.
Checksum: 6BA64A7019911508

FASTA20623,884
        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 

« Hide

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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.
PIRA36177.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CD2X-ray2.20A1-206[»]
1DAJX-ray2.30A1-206[»]
1DYRX-ray1.86A1-206[»]
1E26X-ray2.00A1-206[»]
1KLKX-ray2.30A1-206[»]
1LY3X-ray1.90A1-206[»]
1LY4X-ray2.10A1-206[»]
1S3YX-ray2.25A1-206[»]
1VJ3X-ray2.10A2-206[»]
2CD2X-ray1.90A1-206[»]
2FZHX-ray2.10A1-206[»]
2FZIX-ray1.60A1-206[»]
3CD2X-ray2.50A1-206[»]
3NZ6X-ray2.00X1-206[»]
3NZ9X-ray1.80X1-206[»]
3NZAX-ray1.90X1-206[»]
3NZBX-ray1.45X1-206[»]
3NZCX-ray2.00X1-206[»]
3TD8X-ray1.80A1-206[»]
4CD2X-ray2.00A1-206[»]
4G8ZX-ray1.75X3-206[»]
4IXEX-ray1.54D1-206[»]
4IXFX-ray1.70X1-206[»]
4IXGX-ray1.70X1-206[»]
ProteinModelPortalP16184.
SMRP16184. Positions 1-206.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP16184.
ChEMBLCHEMBL1926.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Enzyme and pathway databases

SABIO-RKP16184.
UniPathwayUPA00077; UER00158.

Family and domain databases

Gene3D3.40.430.10. 1 hit.
InterProIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]
PfamPF00186. DHFR_1. 1 hit.
[Graphical view]
PRINTSPR00070. DHFR.
SUPFAMSSF53597. SSF53597. 1 hit.
PROSITEPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP16184.

Entry information

Entry nameDYR_PNECA
AccessionPrimary (citable) accession number: P16184
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: June 11, 2014
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways