Bifunctional dihydrofolate reductase-thymidylate synthase

Preferred order of sections

Names and origin

Protein names

Recommended name:
Bifunctional dihydrofolate reductase-thymidylate synthase PIRNR PIRNR000389

Gene names

Name:	DHFR-TS PDB 3QG2 PDB 3JSU
ORF Names:	V1/S PDB 3QG2 PDB 3JSU

Organism

Plasmodium falciparum PDB 3QG2

Taxonomic identifier

5833 [NCBI]

Taxonomic lineage

Eukaryota › Alveolata › Apicomplexa › Aconoidasida › Haemosporida › Plasmodium › Plasmodium (Laverania)

Protein attributes

Sequence length	608 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function

Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism By similarity. PIRNR PIRNR000389

Pathway

Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1. PIRNR PIRNR000389

Sequence similarities

In the C-terminal section; belongs to the thymidylate synthase family. PIRNR PIRNR000389

In the N-terminal section; belongs to the dihydrofolate reductase family. PIRNR PIRNR000389

Ontologies

Keywords
Biological process	Nucleotide biosynthesis PIRNR PIRNR000389 One-carbon metabolism PIRNR PIRNR000389
Ligand	NADP PDB 3QG2 Nucleotide-binding PDB 3QG2
Molecular function	Methyltransferase PIRNR PIRNR000389 Oxidoreductase PIRNR PIRNR000389 Transferase
Technical term	3D-structure PDB 3QG2 PDB 4DP3 PDB 4DPH
Gene Ontology (GO)
Biological_process	dTMP biosynthetic process Inferred from electronic annotation. Source: InterPro glycine biosynthetic process Inferred from electronic annotation. Source: InterPro one-carbon metabolic process Inferred from electronic annotation. Source: UniProtKB-KW tetrahydrofolate biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway
Molecular_function	dihydrofolate reductase activity Inferred from electronic annotation. Source: InterPro nucleotide binding Inferred from electronic annotation. Source: UniProtKB-KW thymidylate synthase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Regions

Nucleotide binding

44 – 45

2

NADP PDB 3QG2

Nucleotide binding

106 – 108

3

NADP PDB 3QG2

Nucleotide binding

128 – 130

3

NADP PDB 3QG2

Nucleotide binding

166 – 168

3

NADP PDB 3QG2

Sites

Active site

490

1

By similarity PIRSR PIRSR000389-1

Binding site

16

1

NADP; via amide nitrogen and carbonyl oxygen PDB 3QG2

Binding site

40

1

NADP; via carbonyl oxygen PDB 3QG2

Binding site

144

1

NADP; via carbonyl oxygen PDB 3QG2

Binding site

172

1

NADP PDB 3QG2

Sequences

Sequence

Length

Mass (Da)

Tools

D9N170 [UniParc].

Last modified October 5, 2010. Version 1.
Checksum: 544ED69133C63613
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FASTA

608

71,816

        10         20         30         40         50         60 
MMEQVCDVFD IYAICACCKV ESKNEGKKNE VFNNYTFRGL GNKGVLPWKC ISLDMKYFRA 

        70         80         90        100        110        120 
VTTYVNESKY EKLKYKRCKY LNKETVDNVN DMPNSKKLQN VVVMGRTNWE SIPKKFKPLS 

       130        140        150        160        170        180 
NRINVILSRT LKKEDFDEDV YIINKVEDLI VLLGKLNYYK CFILGGSVVY QEFLEKKLIK 

       190        200        210        220        230        240 
KIYFTRINST YECDVFFPEI NENEYQIISV SDVYTSNNTT LDFIIYKKTN NKMLNEQNCI 

       250        260        270        280        290        300 
KGEEKNNDMP LKNDDKDTCH MKKLTEFYKN VDKYKINYEN DDDDEEEDDF VYFNFNKEKE 

       310        320        330        340        350        360 
EKNKNSIHPN DFQIYNSLKY KYHPEYQYLN IIYDIMMNGN KQSDRTGVGV LSKFGYIMKF 

       370        380        390        400        410        420 
DLSQYFPLLT TKKLFLRGII EELLWFIRGE TNGNTLLNKN VRIWEANGTR EFLDNRKLFH 

       430        440        450        460        470        480 
REVNDLGPIY GFQWRHFGAE YTNMYDNYEN KGVDQLKNII NLIKNDPTSR RILLCAWNVK 

       490        500        510        520        530        540 
DLDQMALPPC HILCQFYVFD GKLSCIMYQR SCDLGLGVPF NIASYSIFTH MIAQVCNLQP 

       550        560        570        580        590        600 
AQFIHVLGNA HVYNNHIDSL KIQLNRIPYP FPTLKLNPDI KNIEDFTISD FTIQNYVHHE 


KISMDMAA

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References

[1]

"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.

[2]

"Malarial dihydrofolate reductase as a paradigm for drug development against a resistance-compromised target."
Yuthavong Y., Tarnchompoo B., Vilaivan T., Chitnumsub P., Kamchonwongpaisan S., Charman S.A., McLennan D.N., White K.L., Vivas L., Bongard E., Thongphanchang C., Taweechai S., Vanichtanankul J., Rattanajak R., Arwon U., Fantauzzi P., Yuvaniyama J., Charman W.N., Matthews D.
Proc. Natl. Acad. Sci. U.S.A. 109:16823-16828(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.38 ANGSTROMS).

Cross-references

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
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	[»]

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Enzyme and pathway databases

UniPathway

UPA00077; UER00158.

Family and domain databases

Gene3D

3.30.572.10. 1 hit.
3.40.430.10. 1 hit.

HAMAP

MF_00008. Thymidy_synth_bact.

InterPro

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]

Pfam

PF00186. DHFR_1. 1 hit.
PF00303. Thymidylat_synt. 1 hit.
[Graphical view]

PIRSF

PIRSF000389. DHFR-TS. 1 hit.

PRINTS

PR00108. THYMDSNTHASE.

SUPFAM

SSF53597. SSF53597. 1 hit.
SSF55831. Thymidylat_synth_C. 1 hit.

TIGRFAMs

TIGR03284. thym_sym. 1 hit.

PROSITE

PS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

D9N170.

Entry information

Entry name

D9N170_PLAFA

Accession

Primary (citable) accession number: D9N170

Entry history

Integrated into UniProtKB/TrEMBL:	October 5, 2010
Last sequence update:	October 5, 2010
Last modified:	May 1, 2013
This is version 23 of the entry and version 1 of the sequence. [Complete history]

Entry status

Unreviewed (UniProtKB/TrEMBL)