Reviewed, UniProtKB/Swiss-Prot Q01782 (PTR1_LEIMA)

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:	HMTXR
ORF Names:	LmjF23.0270, L1063.01

Organism

Leishmania major

Taxonomic identifier

5664 [NCBI]

Taxonomic lineage

Eukaryota › Euglenozoa › Kinetoplastida › Trypanosomatidae › Leishmania

Protein attributes

Sequence length	288 AA.
Sequence status	Complete.
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). Ref.4
Catalytic activity	5,6,7,8-tetrahydrobiopterin + 2 NADP+ = biopterin + 2 NADPH.
Pathway	Cofactor biosynthesis; tetrahydrobiopterin biosynthesis; tetrahydrobiopterin from biopterin: step 1/1. Ref.7
Subunit structure	Homotetramer. Ref.5
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 – 288

288

Pteridine reductase 1

PRO_0000054753

Regions

Nucleotide binding

17 – 40

24

NADP By similarity

Sites

Active site

194

1

Proton acceptor

Binding site

175

1

Substrate

Experimental info

Sequence conflict

162

1

F → V in CAJ03998. Ref.3

Secondary structure

1

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288

Helix Strand Turn

Details...

Beta strand

8 – 11

4

Helix

17 – 28

12

Beta strand

32 – 39

8

Helix

41 – 54

14

Beta strand

59 – 63

5

Beta strand

67 – 69

3

Helix

85 – 100

16

Beta strand

105 – 108

4

Helix

134 – 147

14

Helix

149 – 163

15

Helix

167 – 169

3

Beta strand

174 – 179

6

Turn

182 – 185

4

Helix

192 – 212

21

Helix

213 – 215

3

Beta strand

217 – 227

11

Helix

230 – 232

3

Helix

235 – 242

8

Turn

246 – 249

4

Helix

254 – 265

12

Helix

267 – 269

3

Beta strand

276 – 280

5

Helix

283 – 285

3

Sequences

	Sequence		Length	Mass (Da)
	Q01782-1 [UniParc]. Last modified May 27, 2002. Version 2. Checksum: B8F6FC23018367E0	FASTA	288	30,457
	10 20 30 40 50 60 MTAPTVPVAL VTGAAKRLGR SIAEGLHAEG YAVCLHYHRS AAEANALSAT LNARRPNSAI 70 80 90 100 110 120 TVQADLSNVA TAPVSGADGS APVTLFTRCA ELVAACYTHW GRCDVLVNNA SSFYPTPLLR 130 140 150 160 170 180 NDEDGHEPCV GDREAMETAT ADLFGSNAIA PYFLIKAFAH RFAGTPAKHR GTNYSIINMV 190 200 210 220 230 240 DAMTNQPLLG YTIYTMAKGA LEGLTRSAAL ELAPLQIRVN GVGPGLSVLV DDMPPAVWEG 250 260 270 280 HRSKVPLYQR DSSAAEVSDV VIFLCSSKAK YITGTCVKVD GGYSLTRA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A member of the aldoketo reductase family confers methotrexate resistance in Leishmania." Callahan H.L., Beverley S.M. J. Biol. Chem. 267:24165-24168(1992) [PubMed: 1339441] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: MHOM/IR/83/Lt252 / CC-1.
[2]	Callahan H.L., Beverley S.M. Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 162-171.
[3]	"The genome of the kinetoplastid parasite, Leishmania major." Ivens A.C., Peacock C.S., Worthey E.A., Murphy L., Aggarwal G., Berriman M., Sisk E., Rajandream M.A., Adlem E., Aert R., Anupama A., Apostolou Z., Attipoe P., Bason N., Bauser C., Beck A., Beverley S.M., Bianchettin G. , Borzym K., Bothe G., Bruschi C.V., Collins M., Cadag E., Ciarloni L., Clayton C., Coulson R.M.R., Cronin A., Cruz A.K., Davies R.M., De Gaudenzi J., Dobson D.E., Duesterhoeft A., Fazelina G., Fosker N., Frasch A.C., Fraser A., Fuchs M., Gabel C., Goble A., Goffeau A., Harris D., Hertz-Fowler C., Hilbert H., Horn D., Huang Y., Klages S., Knights A., Kube M., Larke N., Litvin L., Lord A., Louie T., Marra M., Masuy D., Matthews K., Michaeli S., Mottram J.C., Mueller-Auer S., Munden H., Nelson S., Norbertczak H., Oliver K., O'neil S., Pentony M., Pohl T.M., Price C., Purnelle B., Quail M.A., Rabbinowitsch E., Reinhardt R., Rieger M., Rinta J., Robben J., Robertson L., Ruiz J.C., Rutter S., Saunders D., Schaefer M., Schein J., Schwartz D.C., Seeger K., Seyler A., Sharp S., Shin H., Sivam D., Squares R., Squares S., Tosato V., Vogt C., Volckaert G., Wambutt R., Warren T., Wedler H., Woodward J., Zhou S., Zimmermann W., Smith D.F., Blackwell J.M., Stuart K.D., Barrell B.G., Myler P.J. Science 309:436-442(2005) [PubMed: 16020728] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: MHOM/IL/81/Friedlin.
[4]	"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.
[5]	"The roles of pteridine reductase 1 and dihydrofolate reductase-thymidylate synthase in pteridine metabolism in the protozoan parasite Leishmania major." Nare B., Hardy L.W., Beverley S.M. J. Biol. Chem. 272:13883-13891(1997) [PubMed: 9153248] [Abstract] Cited for: SUBUNIT. Strain: MHOM/IR/83/Lt252.
[6]	"Pteridine reductase mechanism correlates pterin metabolism with drug resistance in trypanosomatid parasites." Gourley D.G., Schuettelkopf A.W., Leonard G.A., Luba J., Hardy L.W., Beverley S.M., Hunter W.N. Nat. Struct. Biol. 8:521-525(2001) [PubMed: 11373620] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH NADP AND SUBSTRATE.
[7]	"Leishmania major pteridine reductase 1 belongs to the short chain dehydrogenase family: stereochemical and kinetic evidence." Luba J., Nare B., Liang P.-H., Anderson K.S., Beverley S.M., Hardy L.W. Biochemistry 37:4093-4104(1998) [PubMed: 9521731] [Abstract] Cited for: PATHWAY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L01699 Genomic DNA. Translation: AAA29249.2.
CT005262 Genomic DNA. Translation: CAJ03998.1.

PIR

A45168.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1E7W	X-ray	1.75	A/B	1-288	[»]
1E92	X-ray	2.20	A/B/C/D	1-288	[»]
1W0C	X-ray	2.60	A/B/C/D/E/F/G/H	1-288	[»]
2BF7	X-ray	2.40	A/B/C/D	1-288	[»]
2BFA	X-ray	2.70	A/B/C/D	1-288	[»]
2BFM	X-ray	2.60	A/B/C/D	1-288	[»]
2BFO	X-ray	2.60	A/B/C/D	1-288	[»]
2BFP	X-ray	2.55	A/B/C/D	1-288	[»]
2QHX	X-ray	2.61	A/B/C/D	1-288	[»]
3H4V	X-ray	2.40	A/B/C/D/E/F/G/H	1-288	[»]

ModBase

Search...

Genome annotation databases

GenomeReviews

Gene locus PTR1 in contig CT005262_GR.

Phylogenomic databases

HOGENOM

HBG750976.

Enzyme and pathway databases

BRENDA

1.5.1.33. 19061.

Family and domain databases

InterPro

IPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
IPR014058. Pteridine_reductase.
IPR020904. Sc_DH/Rdtase_CS.
[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_LEIMA

Accession

Primary (citable) accession number: Q01782
Secondary accession number(s): Q4QBE7, Q9U1F8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	May 27, 2002
Last modified:	February 9, 2010
This is version 73 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)