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D9N170

- D9N170_PLAFA

UniProt

D9N170 - D9N170_PLAFA

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Protein
Bifunctional dihydrofolate reductase-thymidylate synthase
Gene
DHFR-TS, V1/S
Organism
Plasmodium falciparum
Status
Unreviewed - Annotation score: 4 out of 5 - Experimental evidence at protein leveli

Functioni

Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism By similarity.UniRule annotation

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei16 – 161NADP; via amide nitrogen and carbonyl oxygenImported
Binding sitei40 – 401NADP; via carbonyl oxygenImported
Binding sitei144 – 1441NADP; via carbonyl oxygenImported
Binding sitei345 – 3451PhosphateImported
Active sitei490 – 4901 By similarityUniRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi44 – 452NADPImported
Nucleotide bindingi106 – 1083NADPImported
Nucleotide bindingi127 – 1304NADPImported
Nucleotide bindingi165 – 1728NADPImported

GO - Molecular functioni

  1. dihydrofolate reductase activity Source: InterPro
  2. nucleotide binding Source: UniProtKB-KW
  3. thymidylate synthase activity Source: InterPro

GO - Biological processi

  1. dTMP biosynthetic process Source: InterPro
  2. glycine 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

MethyltransferaseUniRule annotation, OxidoreductaseUniRule annotation, Transferase

Keywords - Biological processi

Nucleotide biosynthesisUniRule annotation, One-carbon metabolismUniRule annotation

Keywords - Ligandi

NADPImported, Nucleotide-bindingImported

Enzyme and pathway databases

ReactomeiREACT_192655. G1/S-Specific Transcription.
UniPathwayiUPA00077; UER00158.

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional dihydrofolate reductase-thymidylate synthaseUniRule annotation
Gene namesi
Name:DHFR-TSImported
ORF Names:V1/SImported
OrganismiPlasmodium falciparumImported
Taxonomic identifieri5833 [NCBI]
Taxonomic lineageiEukaryotaAlveolataApicomplexaAconoidasidaHaemosporidaPlasmodiumPlasmodium (Laverania)

Structurei

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3JSUX-ray2.70A/B1-608[»]
3QG2X-ray2.30A/B1-608[»]
4DP3X-ray2.40A/B1-608[»]
4DPHX-ray2.38A/B1-608[»]

Miscellaneous databases

EvolutionaryTraceiD9N170.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni470 – 4712Phosphate bindingImported
Regioni510 – 5112Phosphate bindingImported

Sequence similaritiesi

In the C-terminal section; belongs to the thymidylate synthase family.UniRule annotation
In the N-terminal section; belongs to the dihydrofolate reductase family.UniRule annotation

Family and domain databases

Gene3Di3.30.572.10. 1 hit.
3.40.430.10. 1 hit.
HAMAPiMF_00008. Thymidy_synth_bact.
InterProiIPR024072. DHFR-like_dom.
IPR012262. DHFR-TS.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
IPR023451. Thymidate_synth/dCMP_Mease.
IPR000398. Thymidylate_synthase.
IPR020940. Thymidylate_synthase_AS.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
PF00303. Thymidylat_synt. 1 hit.
[Graphical view]
PIRSFiPIRSF000389. DHFR-TS. 1 hit.
PRINTSiPR00108. THYMDSNTHASE.
SUPFAMiSSF53597. SSF53597. 1 hit.
SSF55831. SSF55831. 1 hit.
TIGRFAMsiTIGR03284. thym_sym. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

D9N170-1 [UniParc]FASTAAdd to Basket

« Hide

MMEQVCDVFD IYAICACCKV ESKNEGKKNE VFNNYTFRGL GNKGVLPWKC    50
ISLDMKYFRA VTTYVNESKY EKLKYKRCKY LNKETVDNVN DMPNSKKLQN 100
VVVMGRTNWE SIPKKFKPLS NRINVILSRT LKKEDFDEDV YIINKVEDLI 150
VLLGKLNYYK CFILGGSVVY QEFLEKKLIK KIYFTRINST YECDVFFPEI 200
NENEYQIISV SDVYTSNNTT LDFIIYKKTN NKMLNEQNCI KGEEKNNDMP 250
LKNDDKDTCH MKKLTEFYKN VDKYKINYEN DDDDEEEDDF VYFNFNKEKE 300
EKNKNSIHPN DFQIYNSLKY KYHPEYQYLN IIYDIMMNGN KQSDRTGVGV 350
LSKFGYIMKF DLSQYFPLLT TKKLFLRGII EELLWFIRGE TNGNTLLNKN 400
VRIWEANGTR EFLDNRKLFH REVNDLGPIY GFQWRHFGAE YTNMYDNYEN 450
KGVDQLKNII NLIKNDPTSR RILLCAWNVK DLDQMALPPC HILCQFYVFD 500
GKLSCIMYQR SCDLGLGVPF NIASYSIFTH MIAQVCNLQP AQFIHVLGNA 550
HVYNNHIDSL KIQLNRIPYP FPTLKLNPDI KNIEDFTISD FTIQNYVHHE 600
KISMDMAA 608
Length:608
Mass (Da):71,816
Last modified:October 5, 2010 - v1
Checksum:i544ED69133C63613
GO

Cross-referencesi

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3JSU X-ray 2.70 A/B 1-608 [» ]
3QG2 X-ray 2.30 A/B 1-608 [» ]
4DP3 X-ray 2.40 A/B 1-608 [» ]
4DPH X-ray 2.38 A/B 1-608 [» ]
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Enzyme and pathway databases

UniPathwayi UPA00077 ; UER00158 .
Reactomei REACT_192655. G1/S-Specific Transcription.

Miscellaneous databases

EvolutionaryTracei D9N170.

Family and domain databases

Gene3Di 3.30.572.10. 1 hit.
3.40.430.10. 1 hit.
HAMAPi MF_00008. Thymidy_synth_bact.
InterProi IPR024072. DHFR-like_dom.
IPR012262. DHFR-TS.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
IPR023451. Thymidate_synth/dCMP_Mease.
IPR000398. Thymidylate_synthase.
IPR020940. Thymidylate_synthase_AS.
[Graphical view ]
Pfami PF00186. DHFR_1. 1 hit.
PF00303. Thymidylat_synt. 1 hit.
[Graphical view ]
PIRSFi PIRSF000389. DHFR-TS. 1 hit.
PRINTSi PR00108. THYMDSNTHASE.
SUPFAMi SSF53597. SSF53597. 1 hit.
SSF55831. SSF55831. 1 hit.
TIGRFAMsi TIGR03284. thym_sym. 1 hit.
PROSITEi PS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Preclinical evaluation of the antifolate QN254, 5-chloro- N'6'-(2,5-dimethoxy-benzyl)-quinazoline-2,4,6-triamine, as an antimalarial drug candidate."
    Nzila A., Rottmann M., Chitnumsub P., Kiara S.M., Kamchonwongpaisan S., Maneeruttanarungroj C., Taweechai S., Yeung B.K., Goh A., Lakshminarayana S.B., Zou B., Wong J., Ma N.L., Weaver M., Keller T.H., Dartois V., Wittlin S., Brun R., Yuthavong Y., Diagana T.T.
    Antimicrob. Agents Chemother. 54:2603-2610(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) IN COMPLEX WITH NADP.
  2. "Trypanosomal dihydrofolate reductase reveals natural antifolate resistance."
    Vanichtanankul J., Taweechai S., Yuvaniyama J., Vilaivan T., Chitnumsub P., Kamchonwongpaisan S., Yuthavong Y.
    ACS Chem. Biol. 6:905-911(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH NADP.
  3. Cited for: X-RAY CRYSTALLOGRAPHY (2.38 ANGSTROMS) IN COMPLEX WITH NADP AND PHOSPHATE.

Entry informationi

Entry nameiD9N170_PLAFA
AccessioniPrimary (citable) accession number: D9N170
Entry historyi
Integrated into UniProtKB/TrEMBL: October 5, 2010
Last sequence update: October 5, 2010
Last modified: September 3, 2014
This is version 31 of the entry and version 1 of the sequence. [Complete history]
Entry statusiUnreviewed (UniProtKB/TrEMBL)

Miscellaneousi

Keywords - Technical termi

3D-structureImported

External Data

Dasty 3

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