Reviewed, UniProtKB/Swiss-Prot P42556 (PTR1_LEITA)

Names and origin

Protein names

Recommended name:
    Pteridine reductase 1
    EC=1.5.1.33
Alternative name(s):
    H region methotrexate resistance protein

Gene names

Name:	PTR1
Synonyms:	LTDH

Organism

Leishmania tarentolae (Sauroleishmania tarentolae)

Taxonomic identifier

5689 [NCBI]

Taxonomic lineage

Eukaryota › Euglenozoa › Kinetoplastida › Trypanosomatidae › Leishmania › lizard Leishmania

Protein attributes

Sequence length	289 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Exhibits a NADPH-dependent biopterin reductase activity. Has good activity with folate and significant activity with dihydrofolate and dihydrobiopterin, but not with quinonoid dihydrobiopterin. Confers resistance to methotrexate (MTX).
Catalytic activity	5,6,7,8-tetrahydrobiopterin + 2 NADP(+) = biopterin + 2 NADPH.
Pathway	Cofactor biosynthesis; tetrahydrobiopterin biosynthesis; tetrahydrobiopterin from biopterin: step 1/1.
Subunit structure	Homotetramer By similarity.
Sequence similarities	Belongs to the short-chain dehydrogenases/reductases (SDR) family.

Ontologies

Keywords
Biological process	Methotrexate resistance
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW response to methotrexate Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	binding Inferred from electronic annotation. Source: InterPro pteridine reductase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 289

289

Pteridine reductase 1

PRO_0000054754

Regions

Nucleotide binding

14 – 41

28

NADP

Nucleotide binding

195 – 199

5

NADP

Sites

Active site

195

1

Proton acceptor By similarity

Binding site

176

1

Substrate By similarity

Secondary structure

1

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289

Helix Strand Turn

Details...

Beta strand

9 – 12

4

Turn

13 – 16

4

Helix

18 – 29

12

Beta strand

33 – 40

8

Helix

42 – 55

14

Beta strand

60 – 64

5

Beta strand

68 – 70

3

Helix

86 – 101

16

Beta strand

106 – 109

4

Helix

136 – 148

13

Helix

150 – 164

15

Helix

168 – 170

3

Beta strand

176 – 180

5

Beta strand

185 – 187

3

Helix

193 – 213

21

Turn

214 – 217

4

Beta strand

219 – 229

11

Helix

236 – 243

8

Turn

247 – 250

4

Helix

255 – 266

12

Helix

268 – 270

3

Beta strand

277 – 281

5

Helix

284 – 286

3

Sequences

	Sequence		Length	Mass (Da)
	P42556-1 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 1149EE08968D0310	FASTA	289	30,744
	10 20 30 40 50 60 MTTSPTAPVA LVTGAAKRLG SSIAEALHAE GYTVCLHYHR SAADASTLAA TLNARRPNSA 70 80 90 100 110 120 ITVQADLSNV ATASFSETDG SVPVTLFSRC SALVDACYMH WGRCDVLVNN ASSFYPTPLL 130 140 150 160 170 180 RKDAGEGGSS VGDKESLEVA AADLFGSNAI APYFLIKAFA QRVADTRAEQ RGTSYSIVNM 190 200 210 220 230 240 VDAMTSQPLL GYTMYTMAKE ALEGLTRSAA LELASLQIRV NGVSPGLSVL PDDMPFSVQE 250 260 270 280 DYRRKVPLYQ RNSSAEEVSD VVIFLCSPKA KYITGTCIKV DGGYSLTRA

References

[1]	"A novel antifolate resistance gene on the amplified H circle of Leishmania." Papadopoulou B., Roy G., Ouellette M. EMBO J. 11:3601-3608(1992) [PubMed: 1396560] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: TarII.
[2]	"PTR1: a reductase mediating salvage of oxidized pteridines and methotrexate resistance in the protozoan parasite Leishmania major." Bello A.R., Nare B., Freedman D., Hardy L.W., Beverley S.M. Proc. Natl. Acad. Sci. U.S.A. 91:11442-11446(1994) [PubMed: 7972081] [Abstract] Cited for: FUNCTION.
[3]	"Structure of pteridine reductase (PTR1) from Leishmania tarentolae." Zhao H., Bray T., Ouellette M., Zhao M., Ferre R.A., Matthews D., Whiteley J.M., Varughese K.I. Acta Crystallogr. D 59:1539-1544(2003) [PubMed: 12925782] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.86 ANGSTROMS) IN COMPLEX WITH NADP.

Cross-references

Sequence databases

EMBLGenBankDDBJ

Z11978 Genomic DNA. Translation: CAA78031.1.

PIR

S25286.

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1P33	X-ray	2.86	A/B/C/D	1-289	[»]

ModBase

Search...

Family and domain databases

InterPro

IPR002198. DHase_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DHase.
IPR016040. NAD(P)-bd.
IPR014058. Pteridine_reductase.
[Graphical view]

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

PANTHER

PTHR19410. ADH_short_C2. 1 hit.

Pfam

PF00106. adh_short. 1 hit.
[Graphical view]

PRINTS

PR00081. GDHRDH.
PR00080. SDRFAMILY.

TIGRFAMs

TIGR02685. pter_reduc_Leis. 1 hit.

PROSITE

PS00061. ADH_SHORT. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

PTR1_LEITA

Accession

Primary (citable) accession number: P42556

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	November 25, 2008
This is version 56 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)