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P16184

- DYR_PNECA

UniProt

P16184 - DYR_PNECA

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Protein

Dihydrofolate reductase

Gene
N/A
Organism
Pneumocystis carinii
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli

Functioni

Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.

Catalytic activityi

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.PROSITE-ProRule annotation

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei12 – 121NADP; via amide nitrogen and carbonyl oxygen5 Publications
Binding sitei75 – 751Substrate

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi18 – 247NADP5 Publications
Nucleotide bindingi59 – 613NADP5 Publications
Nucleotide bindingi81 – 833NADP5 Publications
Nucleotide bindingi124 – 1318NADP5 Publications

GO - Molecular functioni

  1. dihydrofolate reductase activity Source: UniProtKB-EC
  2. NADP binding Source: InterPro

GO - Biological processi

  1. glycine biosynthetic process Source: InterPro
  2. nucleotide biosynthetic process Source: InterPro
  3. one-carbon metabolic process Source: UniProtKB-KW
  4. tetrahydrofolate biosynthetic process Source: UniProtKB-UniPathway
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

One-carbon metabolism

Keywords - Ligandi

NADP

Enzyme and pathway databases

SABIO-RKP16184.
UniPathwayiUPA00077; UER00158.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydrofolate reductase (EC:1.5.1.3)
OrganismiPneumocystis carinii
Taxonomic identifieri4754 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaTaphrinomycotinaPneumocystidomycetesPneumocystidaceaePneumocystis

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 206206Dihydrofolate reductasePRO_0000186376Add
BLAST

Interactioni

Structurei

Secondary structure

1
206
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi3 – 53
Beta strandi7 – 148
Beta strandi18 – 214
Helixi30 – 4112
Helixi47 – 493
Beta strandi51 – 588
Helixi59 – 646
Helixi67 – 693
Beta strandi75 – 806
Beta strandi89 – 913
Beta strandi93 – 975
Helixi98 – 10811
Beta strandi111 – 12212
Helixi126 – 1349
Beta strandi138 – 1469
Beta strandi153 – 1553
Helixi163 – 1653
Turni166 – 1683
Beta strandi169 – 1713
Helixi174 – 1818
Beta strandi190 – 1923
Beta strandi195 – 2039

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliP16184.
SMRiP16184. Positions 1-206.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP16184.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini6 – 204199DHFRPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni32 – 376Substrate binding

Sequence similaritiesi

Belongs to the dihydrofolate reductase family.Curated
Contains 1 DHFR (dihydrofolate reductase) domain.PROSITE-ProRule annotation

Family and domain databases

Gene3Di3.40.430.10. 1 hit.
InterProiIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
[Graphical view]
PRINTSiPR00070. DHFR.
SUPFAMiSSF53597. SSF53597. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P16184-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MNQQKSLTLI VALTTSYGIG RSNSLPWKLK KEISYFKRVT SFVPTFDSFE
60 70 80 90 100
SMNVVLMGRK TWESIPLQFR PLKGRINVVI TRNESLDLGN GIHSAKSLDH
110 120 130 140 150
ALELLYRTYG SESSVQINRI FVIGGAQLYK AAMDHPKLDR IMATIIYKDI
160 170 180 190 200
HCDVFFPLKF RDKEWSSVWK KEKHSDLESW VGTKVPHGKI NEDGFDYEFE

MWTRDL
Length:206
Mass (Da):23,884
Last modified:April 1, 1990 - v1
Checksum:i6BA64A7019911508
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M26495 Genomic DNA. Translation: AAA33787.1.
M26496 mRNA. Translation: AAA33788.1.
PIRiA36177.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M26495 Genomic DNA. Translation: AAA33787.1 .
M26496 mRNA. Translation: AAA33788.1 .
PIRi A36177.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
3TD8 X-ray 1.80 A 1-206 [» ]
4CD2 X-ray 2.00 A 1-206 [» ]
4G8Z X-ray 1.75 X 3-206 [» ]
4IXE X-ray 1.54 D 1-206 [» ]
4IXF X-ray 1.70 X 1-206 [» ]
4IXG X-ray 1.70 X 1-206 [» ]
ProteinModelPortali P16184.
SMRi P16184. Positions 1-206.
ModBasei Search...
MobiDBi Search...

Chemistry

BindingDBi P16184.
ChEMBLi CHEMBL2097173.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Enzyme and pathway databases

UniPathwayi UPA00077 ; UER00158 .
SABIO-RK P16184.

Miscellaneous databases

EvolutionaryTracei P16184.

Family and domain databases

Gene3Di 3.40.430.10. 1 hit.
InterProi IPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view ]
Pfami PF00186. DHFR_1. 1 hit.
[Graphical view ]
PRINTSi PR00070. DHFR.
SUPFAMi SSF53597. SSF53597. 1 hit.
PROSITEi PS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiDYR_PNECA
AccessioniPrimary (citable) accession number: P16184
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: October 29, 2014
This is version 95 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3