A7UD81 (A7UD81_PLAFA) Unreviewed, UniProtKB/TrEMBL

Names and origin

Protein names

Recommended name:
Bifunctional dihydrofolate reductase-thymidylate synthase PIRNR PIRNR000389

Gene names

Name:	DHFR-TS EMBL ABU43153.1
Synonyms:	dhfr-ts EMBL ACG59401.1

Organism

Plasmodium falciparum EMBL ABU43153.1

Taxonomic identifier

5833 [NCBI]

Taxonomic lineage

cellular organisms › 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 3QGT Nucleotide-binding PDB 3QGT
Molecular function	Methyltransferase PIRNR PIRNR000389 Oxidoreductase PIRNR PIRNR000389 Transferase
Technical term	3D-structure PDB 4DPD PDB 3UM8 PDB 3UM6 PDB 3QGT PDB 3UM5
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 3QGT
	Nucleotide binding	106 – 108	3	NADP PDB 3QGT
	Nucleotide binding	128 – 130	3	NADP PDB 3QGT
	Nucleotide binding	167 – 168	2	NADP PDB 3QGT
Sites
	Active site	490	1	By similarity PIRSR PIRSR000389-1
	Binding site	16	1	NADP; via amide nitrogen and carbonyl oxygen PDB 3QGT
	Binding site	40	1	NADP; via carbonyl oxygen PDB 3QGT
	Binding site	144	1	NADP; via carbonyl oxygen PDB 3QGT
	Binding site	172	1	NADP PDB 3QGT

Sequences

	Sequence		Length	Mass (Da)
	A7UD81 [UniParc]. Last modified October 2, 2007. Version 1. Checksum: 26FD4BB4A5F1F4A7	FASTA	608	71,737
	10 20 30 40 50 60 MMEQVCDVFD IYAICACCKV ESKNEGKKNE VFNNYTFRGL GNKGVLPWKC NSLDMKYFCA 70 80 90 100 110 120 VTTYVNESKY EKLKYKRCKY LNKETVDNVN DMPNSKKLQN VVVMGRTSWE SIPKKFKPLS 130 140 150 160 170 180 NRINVILSRT LKKEDFDEDV YIINKVEDLI VLLGKLNYYK CFIIGGSVVY 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

References

[1]	"Rapid dissemination of Plasmodium falciparum drug resistance despite strictly controlled antimalarial use." Noranate N., Durand R., Tall A., Marrama L., Spiegel A., Sokhna C., Pradines B., Cojean S., Guillotte M., Bischoff E., Ekala M.T., Bouchier C., Fandeur T., Ariey F., Patarapotikul J., Le Bras J., Trape J.F., Rogier C., Mercereau-Puijalon O. PLoS ONE 2:e139-e139(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE. Strain: 14290 EMBL ABU43153.1, 18308 EMBL ABU43155.1, 44200 EMBL ABU43156.1 and 45700 EMBL ABU43154.1.
[2]	"Analysis of drug resistance genes of Plasmodium falciparum in isolates from Bikaner, India." Garg S., Saxena V., Kochar D., Das A. Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE. Strain: INBK1004 EMBL ACG59401.1.
[3]	"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.
[4]	"Combined spatial limitation around residues 16 and 108 of Plasmodium falciparum dihydrofolate reductase explains resistance to cycloguanil." Vanichtanankul J., Taweechai S., Uttamapinant C., Chitnumsub P., Vilaivan T., Yuthavong Y., Kamchonwongpaisan S. Antimicrob. Agents Chemother. 56:3928-3935(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS).
[5]	"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 (2.50 ANGSTROMS).

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

EU046230 Genomic DNA. Translation: ABU43153.1.
EU046231 Genomic DNA. Translation: ABU43154.1.
EU046232 Genomic DNA. Translation: ABU43155.1.
EU046233 Genomic DNA. Translation: ABU43156.1.
EU682760 Genomic DNA. Translation: ACG59401.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3QGT	X-ray	2.30	A/B	1-608	[»]
3UM5	X-ray	2.40	A/B	1-608	[»]
3UM6	X-ray	2.65	A/B	1-608	[»]
3UM8	X-ray	2.60	A/B	1-608	[»]
4DPD	X-ray	2.50	A/B	1-608	[»]

SMR

A7UD81. Positions 2-231, 283-608.

ModBase

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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

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Other

EvolutionaryTrace

A7UD81.

Entry information

Entry name

A7UD81_PLAFA

Accession

Primary (citable) accession number: A7UD81

Entry history

Integrated into UniProtKB/TrEMBL:	October 2, 2007
Last sequence update:	October 2, 2007
Last modified:	May 1, 2013
This is version 43 of the entry and version 1 of the sequence. [Complete history]

Entry status

Unreviewed (UniProtKB/TrEMBL)