Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P16184

- DYR_PNECA

UniProt

P16184 - DYR_PNECA

Protein

Dihydrofolate reductase

Gene
N/A
Organism
Pneumocystis carinii
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 94 (01 Oct 2014)
      Sequence version 1 (01 Apr 1990)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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

    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

    MNQQKSLTLI VALTTSYGIG RSNSLPWKLK KEISYFKRVT SFVPTFDSFE    50
    SMNVVLMGRK TWESIPLQFR PLKGRINVVI TRNESLDLGN GIHSAKSLDH 100
    ALELLYRTYG SESSVQINRI FVIGGAQLYK AAMDHPKLDR IMATIIYKDI 150
    HCDVFFPLKF RDKEWSSVWK KEKHSDLESW VGTKVPHGKI NEDGFDYEFE 200
    MWTRDL 206
    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 CHEMBL1926.

    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 1, 2014
    This is version 94 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