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Protein

Pteridine reductase 1

Gene

PTR1

Organism
Leishmania tarentolae (Sauroleishmania tarentolae)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at protein leveli

Functioni

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).1 Publication

Catalytic activityi

5,6,7,8-tetrahydrobiopterin + 2 NADP+ = biopterin + 2 NADPH.

Pathwayi: tetrahydrobiopterin biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes tetrahydrobiopterin from biopterin.
Proteins known to be involved in this subpathway in this organism are:
  1. Pteridine reductase 1 (PTR1)
This subpathway is part of the pathway tetrahydrobiopterin biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes tetrahydrobiopterin from biopterin, the pathway tetrahydrobiopterin biosynthesis and in Cofactor biosynthesis.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei176 – 1761SubstrateBy similarity
Active sitei195 – 1951Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi14 – 4128NADP1 PublicationAdd
BLAST
Nucleotide bindingi195 – 1995NADP1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Methotrexate resistance

Keywords - Ligandi

NADP

Enzyme and pathway databases

BRENDAi1.5.1.33. 2956.
UniPathwayiUPA00849; UER00822.

Names & Taxonomyi

Protein namesi
Recommended name:
Pteridine reductase 1 (EC:1.5.1.33)
Alternative name(s):
H region methotrexate resistance protein
Gene namesi
Name:PTR1
Synonyms:LTDH
OrganismiLeishmania tarentolae (Sauroleishmania tarentolae)
Taxonomic identifieri5689 [NCBI]
Taxonomic lineageiEukaryotaEuglenozoaKinetoplastidaTrypanosomatidaeLeishmaniinaeLeishmanializard Leishmania

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 289289Pteridine reductase 1PRO_0000054754Add
BLAST

Interactioni

Subunit structurei

Homotetramer.By similarity

Structurei

Secondary structure

1
289
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi9 – 124Combined sources
Turni13 – 164Combined sources
Helixi18 – 2912Combined sources
Beta strandi33 – 408Combined sources
Helixi42 – 5514Combined sources
Beta strandi60 – 645Combined sources
Beta strandi68 – 703Combined sources
Helixi86 – 10116Combined sources
Beta strandi106 – 1094Combined sources
Helixi136 – 14813Combined sources
Helixi150 – 16415Combined sources
Helixi168 – 1703Combined sources
Beta strandi176 – 1805Combined sources
Beta strandi185 – 1873Combined sources
Helixi193 – 21321Combined sources
Turni214 – 2174Combined sources
Beta strandi219 – 22911Combined sources
Helixi236 – 2438Combined sources
Turni247 – 2504Combined sources
Helixi255 – 26612Combined sources
Helixi268 – 2703Combined sources
Beta strandi277 – 2815Combined sources
Helixi284 – 2863Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1P33X-ray2.86A/B/C/D1-289[»]
ProteinModelPortaliP42556.
SMRiP42556. Positions 4-289.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42556.

Family & Domainsi

Sequence similaritiesi

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR016040. NAD(P)-bd_dom.
IPR014058. Pteridine_reductase.
IPR020904. Sc_DH/Rdtase_CS.
IPR002347. SDR_fam.
[Graphical view]
PANTHERiPTHR24322. PTHR24322. 3 hits.
PRINTSiPR00081. GDHRDH.
PR00080. SDRFAMILY.
SUPFAMiSSF51735. SSF51735. 1 hit.
TIGRFAMsiTIGR02685. pter_reduc_Leis. 1 hit.
PROSITEiPS00061. ADH_SHORT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P42556-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTTSPTAPVA LVTGAAKRLG SSIAEALHAE GYTVCLHYHR SAADASTLAA
60 70 80 90 100
TLNARRPNSA ITVQADLSNV ATASFSETDG SVPVTLFSRC SALVDACYMH
110 120 130 140 150
WGRCDVLVNN ASSFYPTPLL RKDAGEGGSS VGDKESLEVA AADLFGSNAI
160 170 180 190 200
APYFLIKAFA QRVADTRAEQ RGTSYSIVNM VDAMTSQPLL GYTMYTMAKE
210 220 230 240 250
ALEGLTRSAA LELASLQIRV NGVSPGLSVL PDDMPFSVQE DYRRKVPLYQ
260 270 280
RNSSAEEVSD VVIFLCSPKA KYITGTCIKV DGGYSLTRA
Length:289
Mass (Da):30,744
Last modified:November 1, 1995 - v1
Checksum:i1149EE08968D0310
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z11978 Genomic DNA. Translation: CAA78031.1.
PIRiS25286.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z11978 Genomic DNA. Translation: CAA78031.1.
PIRiS25286.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1P33X-ray2.86A/B/C/D1-289[»]
ProteinModelPortaliP42556.
SMRiP42556. Positions 4-289.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

UniPathwayiUPA00849; UER00822.
BRENDAi1.5.1.33. 2956.

Miscellaneous databases

EvolutionaryTraceiP42556.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR016040. NAD(P)-bd_dom.
IPR014058. Pteridine_reductase.
IPR020904. Sc_DH/Rdtase_CS.
IPR002347. SDR_fam.
[Graphical view]
PANTHERiPTHR24322. PTHR24322. 3 hits.
PRINTSiPR00081. GDHRDH.
PR00080. SDRFAMILY.
SUPFAMiSSF51735. SSF51735. 1 hit.
TIGRFAMsiTIGR02685. pter_reduc_Leis. 1 hit.
PROSITEiPS00061. ADH_SHORT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  3. Cited for: X-RAY CRYSTALLOGRAPHY (2.86 ANGSTROMS) IN COMPLEX WITH NADP.

Entry informationi

Entry nameiPTR1_LEITA
AccessioniPrimary (citable) accession number: P42556
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: April 13, 2016
This is version 89 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)

Miscellaneousi

Keywords - Technical termi

3D-structure

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.