PTR1_LEITA
ID PTR1_LEITA Reviewed; 289 AA.
AC P42556;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Pteridine reductase 1;
DE EC=1.5.1.33;
DE AltName: Full=H region methotrexate resistance protein;
GN Name=PTR1; Synonyms=LTDH;
OS Leishmania tarentolae (Sauroleishmania tarentolae).
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania;
OC lizard Leishmania.
OX NCBI_TaxID=5689;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=TarII;
RX PubMed=1396560; DOI=10.1002/j.1460-2075.1992.tb05444.x;
RA Papadopoulou B., Roy G., Ouellette M.;
RT "A novel antifolate resistance gene on the amplified H circle of
RT Leishmania.";
RL EMBO J. 11:3601-3608(1992).
RN [2]
RP FUNCTION.
RX PubMed=7972081; DOI=10.1073/pnas.91.24.11442;
RA Bello A.R., Nare B., Freedman D., Hardy L.W., Beverley S.M.;
RT "PTR1: a reductase mediating salvage of oxidized pteridines and
RT methotrexate resistance in the protozoan parasite Leishmania major.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:11442-11446(1994).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.86 ANGSTROMS) IN COMPLEX WITH NADP.
RX PubMed=12925782; DOI=10.1107/s0907444903013131;
RA Zhao H., Bray T., Ouellette M., Zhao M., Ferre R.A., Matthews D.,
RA Whiteley J.M., Varughese K.I.;
RT "Structure of pteridine reductase (PTR1) from Leishmania tarentolae.";
RL Acta Crystallogr. D 59:1539-1544(2003).
CC -!- FUNCTION: Exhibits a NADPH-dependent biopterin reductase activity. Has
CC good activity with folate and significant activity with dihydrofolate
CC and dihydrobiopterin, but not with quinonoid dihydrobiopterin. Confers
CC resistance to methotrexate (MTX). {ECO:0000269|PubMed:7972081}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + 2 NADP(+) = 2
CC H(+) + L-erythro-biopterin + 2 NADPH; Xref=Rhea:RHEA:19509,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:59560, ChEBI:CHEBI:63931; EC=1.5.1.33;
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrobiopterin biosynthesis;
CC tetrahydrobiopterin from biopterin: step 1/1.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; Z11978; CAA78031.1; -; Genomic_DNA.
DR PIR; S25286; S25286.
DR PDB; 1P33; X-ray; 2.86 A; A/B/C/D=1-289.
DR PDBsum; 1P33; -.
DR AlphaFoldDB; P42556; -.
DR SMR; P42556; -.
DR VEuPathDB; TriTrypDB:LtaPh_2303300; -.
DR PhylomeDB; P42556; -.
DR BRENDA; 1.5.1.33; 2956.
DR SABIO-RK; P42556; -.
DR UniPathway; UPA00849; UER00822.
DR EvolutionaryTrace; P42556; -.
DR GO; GO:0047040; F:pteridine reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0031427; P:response to methotrexate; IEA:UniProtKB-KW.
DR GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR014058; Pteridine_reductase.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR02685; pter_reduc_Leis; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Methotrexate resistance; NADP; Oxidoreductase.
FT CHAIN 1..289
FT /note="Pteridine reductase 1"
FT /id="PRO_0000054754"
FT ACT_SITE 195
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 14..41
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12925782"
FT BINDING 176
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 195..199
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12925782"
FT STRAND 9..12
FT /evidence="ECO:0007829|PDB:1P33"
FT TURN 13..16
FT /evidence="ECO:0007829|PDB:1P33"
FT HELIX 18..29
FT /evidence="ECO:0007829|PDB:1P33"
FT STRAND 33..40
FT /evidence="ECO:0007829|PDB:1P33"
FT HELIX 42..55
FT /evidence="ECO:0007829|PDB:1P33"
FT STRAND 60..64
FT /evidence="ECO:0007829|PDB:1P33"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:1P33"
FT HELIX 86..101
FT /evidence="ECO:0007829|PDB:1P33"
FT STRAND 106..109
FT /evidence="ECO:0007829|PDB:1P33"
FT HELIX 136..148
FT /evidence="ECO:0007829|PDB:1P33"
FT HELIX 150..164
FT /evidence="ECO:0007829|PDB:1P33"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:1P33"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:1P33"
FT STRAND 185..187
FT /evidence="ECO:0007829|PDB:1P33"
FT HELIX 193..213
FT /evidence="ECO:0007829|PDB:1P33"
FT TURN 214..217
FT /evidence="ECO:0007829|PDB:1P33"
FT STRAND 219..229
FT /evidence="ECO:0007829|PDB:1P33"
FT HELIX 236..243
FT /evidence="ECO:0007829|PDB:1P33"
FT TURN 247..250
FT /evidence="ECO:0007829|PDB:1P33"
FT HELIX 255..266
FT /evidence="ECO:0007829|PDB:1P33"
FT HELIX 268..270
FT /evidence="ECO:0007829|PDB:1P33"
FT STRAND 277..281
FT /evidence="ECO:0007829|PDB:1P33"
FT HELIX 284..286
FT /evidence="ECO:0007829|PDB:1P33"
SQ SEQUENCE 289 AA; 30744 MW; 1149EE08968D0310 CRC64;
MTTSPTAPVA LVTGAAKRLG SSIAEALHAE GYTVCLHYHR SAADASTLAA TLNARRPNSA
ITVQADLSNV ATASFSETDG SVPVTLFSRC SALVDACYMH WGRCDVLVNN ASSFYPTPLL
RKDAGEGGSS VGDKESLEVA AADLFGSNAI APYFLIKAFA QRVADTRAEQ RGTSYSIVNM
VDAMTSQPLL GYTMYTMAKE ALEGLTRSAA LELASLQIRV NGVSPGLSVL PDDMPFSVQE
DYRRKVPLYQ RNSSAEEVSD VVIFLCSPKA KYITGTCIKV DGGYSLTRA
