Hidden Markov Models (TIGR)
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniPathway vocabulary mapping
Combined Automated Annotation using Multiple IEA Methods
Dissecting the metabolic roles of pteridine reductase 1 in Trypanosoma brucei and Leishmania major.
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LmPTR1 has NADPH-dependent quinonoid dihydropteridine reductase activity in addition to pteridine reductase activity, with about 20-fold lower efficiency than LmQDPR.
"we demonstrate that there is an NADPH-dependent QDPR activity associated with both TbPTR1 and LmPTR1."
PTR1: a reductase mediating salvage of oxidized pteridines and methotrexate resistance in the protozoan parasite Leishmania major.
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PTR1 is the primary enzyme of pteridine salvage; ptr1- mutants require reduced biopterin.
"The concordance of the biochemical and genetic properties of PTR1 suggests that this is the primary enzyme mediating pteridine salvage."
The roles of pteridine reductase 1 and dihydrofolate reductase-thymidylate synthase in pteridine metabolism in the protozoan parasite Leishmania major.
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PTR1 is a homotetramer and is much less sensitive to methotrexate than DHFR-TS.
"PTR1 exhibited 2000-fold less sensitivity to inhibition by methotrexate than dihydrofolate reductase-thymidylate synthase, suggesting several mechanisms by which PTR1 may compromise antifolate inhibition in wild-type Leishmania and lines bearing PTR1 amplifications."
Leishmania major pteridine reductase 1 belongs to the short chain dehydrogenase family: stereochemical and kinetic evidence.
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PTR1 reduces folate to THF via DHF with DHFR-like stereochemistry and follows an ordered SDR mechanism.
"With folate as a substrate, PTR1 catalyzes two rounds of reduction, yielding 5,6,7, 8-tetrahydrofolate and oxidizing 2 equiv of NADPH."
Pteridine reductase mechanism correlates pterin metabolism with drug resistance in trypanosomatid parasites.
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Crystal structures show a two-step reduction mechanism; the first step is SDR-like and the second is DHFR-like.
"The first reduction uses the generic SDR mechanism, whereas the second shares similarities with the mechanism proposed for DHFR."
A member of the aldoketo reductase family confers methotrexate resistance in Leishmania.
Trypanosoma brucei pteridine reductase 1 is essential for survival in vitro and for virulence in mice.
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TbPTR1, the ISO donor ortholog, is cytosolic by digitonin fractionation.
"PTR1 was recovered exclusively in the cytosolic fraction along with the cytosolic enzyme marker, enolase."
Degradation of pteridine reductase 1 (PTR1) enzyme during growth phase in the protozoan parasite Leishmania donovani.
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L. donovani PTR1-GFP is cytoplasmic and is degraded in stationary phase, which the authors propose is proteasome-mediated.
"Fluorescence microscopy revealed cytoplasmic localization of GFP tagged protein extending to the flagellum in these stationary phase promastigotes, implying that degradation of the protein was not by the usual multivesicular tubule lysosome (MVT) pathway."