Falcon (Edison Scientific) deep research report on rat Qdpr (DHPR/QDPR, UniProt P11348)
-
Falcon confirms gene identity and the core reaction; rat Qdpr is an NAD(H)-dependent oxidoreductase that regenerates tetrahydrobiopterin from quinonoid dihydrobiopterin.
"an NAD(H)-dependent oxidoreductase that catalyzes regeneration of **tetrahydrobiopterin (BH4)** from **quinonoid dihydrobiopterin (qBH2)**"
-
Falcon places Qdpr as the terminal BH4-recycling enzyme that maintains reduced cofactor supply for the aromatic amino acid hydroxylases, the primary function for annotation.
"Qdpr functions in **BH4 recycling**, complementing BH4 de novo synthesis and maintaining reduced cofactor supply for **PAH, TH, and TPH**. This is the primary function most relevant for annotation."
-
Falcon corroborates NADH as the directly observed, physiologic cofactor for rat DHPR.
"Direct structural evidence shows **NADH bound** in the rat DHPR crystal structure and supports NADH as the physiologic electron donor."
-
Falcon notes NADH is kinetically preferred over NADPH in vitro for the rat enzyme, with NADPH a possible contributor in vivo, supporting both nucleotide-binding annotations as cofactor context.
"Older rat biochemical work indicates **NADH is more effective than NADPH in vitro**, while allowing that NADPH may contribute in vivo depending on cellular redox pools."
-
Falcon corroborates the homodimeric quaternary structure underlying the identical protein binding annotation.
"The protein exists as a **dimer in solution**; dimerization is mediated by a **four-helix bundle** formed by helices contributed from each protomer."
-
Falcon supports a predominantly cytosolic localization consistent with soluble BH4 recycling.
"a cell-based study reported wild-type QDPR is mainly **cytoplasmic** (with a mutant showing altered localization)"
GO reference used by source annotation pipeline
-
Source annotation pipeline provenance for Qdpr annotations including 6,7-dihydropteridine reductase activity; NADH binding; NADPH binding; cytoplasm; tetrahydrobiopterin biosynthetic process.
"GO_REF entry used only to trace source annotation method; biological support was assessed from UniProt and cached literature where available."
GO reference used by source annotation pipeline
-
Source annotation pipeline provenance for Qdpr annotations including pteridine-containing compound metabolic process.
"GO_REF entry used only to trace source annotation method; biological support was assessed from UniProt and cached literature where available."
GO reference used by source annotation pipeline
-
Source annotation pipeline provenance for Qdpr annotations including 6,7-dihydropteridine reductase activity.
"GO_REF entry used only to trace source annotation method; biological support was assessed from UniProt and cached literature where available."
GO reference used by source annotation pipeline
-
Source annotation pipeline provenance for Qdpr annotations including 6,7-dihydropteridine reductase activity; cytoplasm.
"GO_REF entry used only to trace source annotation method; biological support was assessed from UniProt and cached literature where available."
Crystal structure of rat liver dihydropteridine reductase
-
For Qdpr, this publication was reviewed as context for identical protein binding.
"DHPR is an alpha/beta protein with a Rossmann-type dinucleotide fold for NADH binding. Insertion of an extra threonine residue in the human enzyme is associated with severe symptoms of a variant form of phenylketonuria and maps to a tightly linked sequence of secondary-structural elements near the dimer interface."
Characterization and nucleotide binding properties of a mutant dihydropteridine reductase containing an aspartate 37-isoleucine replacement
-
For Qdpr, this publication was reviewed as context for NADPH binding.
"Kinetic constants for the interaction of NADH and NADPH with native rat dihydropteridine reductase (DHPR) and an Escherichia coli expressed mutant (D-37-I) have been determined."
Role of aspartate-37 in determining cofactor specificity and binding in rat liver dihydropteridine reductase
-
For Qdpr, this publication supports direct annotations to 6,7-dihydropteridine reductase activity; tetrahydrobiopterin biosynthetic process.
"Full-length rat dihydropteridine reductase (DHPR) cDNAs have been combined with a prokaryotic expression vector and introduced into Escherichia coli."
Regulation of GTP cyclohydrolase I and dihydropteridine reductase in rat pheochromocytoma PC 12 cells
-
For Qdpr, this publication was reviewed as context for cellular response to xenobiotic stimulus.
"The addition of 8-bromo cyclic AMP, forskolin, theophylline, and 3-isobutyl-1-methylxanthine to the medium of PC 12 cells resulted in an increase in GTP cyclohydrolase I activity, but had no effect on dihydropteridine reductase activity, except theophylline which caused a decrease in dihydropteridine reductase activity at 96 h."
The effect of lead and aluminium on rat dihydropteridine reductase
-
For Qdpr, this publication was reviewed as context for response to aluminum ion. Cached PubMed record has no abstract/full text available, so the title is retained with full_text_unavailable.
"The effect of lead and aluminium on rat dihydropteridine reductase"
Structural studies and isolation of cDNA clones providing the complete sequence of rat liver dihydropteridine reductase
-
For Qdpr, this publication supports direct annotations to tetrahydrobiopterin biosynthetic process.
"The cleavage of reductively alkylated rat liver dihydropteridine reductase with cyanogen bromide afforded a mixture of peptides, six of which (CB-1 to CB-6) were isolated and purified by C8 reverse-phase high performance liquid chromatography."
The effect of lead on tetrahydrobiopterin metabolism. A possible mechanism for neurotoxicity
-
For Qdpr, this publication was reviewed as context for response to lead ion.
"The use of low levels of lead in vivo in rats has been found to inhibit dihydropteridine reductase and cause an apparent increase in tetrahydrobiopterin biosynthesis."
Effect of glucagon on phenylalanine metabolism and phenylalanine-degrading enzymes in the rat
-
For Qdpr, this publication was reviewed as context for response to glucagon.
"Glucagon administered subcutaneously to rats for 10 days had no significant effect on liver phenylalanine hydroxylase activity, but induced liver dihydropteridine reductase more than twofold."
Regional and subcellular distribution and some factors in the regulation of reduced pterins in rat brain
-
For Qdpr, this publication supports direct annotations to 6,7-dihydropteridine reductase activity; tetrahydrobiopterin biosynthetic process.
"We have studied the regional and subcellular distribution, functional role, and pharmacology of quinoid dihydropterin reductase (QDPR) and endogenous reduced pterins (PH4) subserving tyrosin hydroxylase (TOH) and tryptophan hydroxylase in the rat brain."
Dihydropteridine reductase activity of adult, fetal and neoplastic tissues
-
For Qdpr, this publication was reviewed as context for liver development.
"Optimal conditions for the assay of dihydropteridine reductase in crude tissue extracts have been developed. Among adult rat tissues, liver and kidney had the highest activity followed by thymus, lung, cerebellum and cerebrum."
The crystallographic structure of a human dihydropteridine reductase NADH binary complex expressed in Escherichia coli by a cDNA constructed from its rat homologue
-
For Qdpr, this publication supports direct annotations to 6,7-dihydropteridine reductase activity.
"A human dihydropteridine reductase (EC 1.6.99.10) has been created from a rat cDNA clone by a single five-oligonucleotide mutagenesis reaction and expressed in good yield in Escherichia coli."
Altered structural and mechanistic properties of mutant dihydropteridine reductases
-
For Qdpr, this publication was reviewed as context for NADH binding.
"Nine single genetic mutants of rat dihydropteridine reductase (EC 1.6.99.7), D37I, W86I, Y146F, Y146H, K150Q, K150I, K150M, N186A, and A133S and one double mutant, Y146F/K150Q, have been engineered, overexpressed in Escherichia coli and their proteins purified."
The comparative interaction of quinonoid (6R)-dihydrobiopterin and an alternative dihydropterin substrate with wild-type and mutant rat dihydropteridine reductases
-
For Qdpr, this publication supports direct annotations to tetrahydrobiopterin biosynthetic process.
"Kinetic parameters and primary deuterium isotope effects have been determined for wild-type dihydropteridine reductase (EC 1.6.99.7) and the Ala133Ser, Lys150Gln, Tyr146His, Tyr146Phe single, and Tyr146Phe/Ala133Ser and Tyr146Phe/Lys150Gln double mutant enzyme forms using the natural substrate, quinonoid (6R)-l-erythro-dihydrobiopterin (qBH2) and an alternate substrate, quinonoid 6,7-dimethyldihydropteridine."