Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 1.1.1.79 extracted from

  • Booth, M.P.; Conners, R.; Rumsby, G.; Brady, R.L.
    Structural basis of substrate specificity in human glyoxylate reductase/hydroxypyruvate reductase (2006), J. Mol. Biol., 360, 178-189.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
expression of His-tagged wild-type and mutant enzymes in Escherichia coli Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
purified detagged recombinant enzyme in ternary complex with product D-glycerate and cofactor NADPH, sitting drop vapour diffusion method, 5.5 mg/ml protein in 20 mM Tris-HCl, pH 8.5, 1 mM 2-mercaptoethanol, 0.2 mM NADPH, and 0.5 mm di-sodium oxalate, mixed with mother liquor, containing 15% w/v PEG 8000, 0.2 M ammonium sulfate, and 0.1 M sodium cacodylate, pH 6.5, to 0.002 ml drops, 18°C, X-ray diffraction structure determination and analysis at 2.2 A resolution Homo sapiens
sitting-drop vapour-diffusipon method. Crystal structure at 2.2 Å resolution. There are four copies of GRHPR in the crystallographic asymmetric unit: in each homodimer, one subunit forms a ternary (enzyme/NADPH/reduced substrate) complex, and the other a binary (enzyme/NADPH) form. The spatial arrangement of the two enzyme domains is the same in binary and ternary forms Homo sapiens

Protein Variants

Protein Variants Comment Organism
G160R site-directed mutagenesis, the mutant shows reduced catalytic activity compared to the wild-type enzyme Homo sapiens
G165D site-directed mutagenesis, the mutant shows reduced catalytic activity compared to the wild-type enzyme Homo sapiens
M322R site-directed mutagenesis, the mutant shows reduced catalytic activity compared to the wild-type enzyme Homo sapiens
R302C site-directed mutagenesis, the mutant shows reduced catalytic activity compared to the wild-type enzyme Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
D-glycerate the enzyme shows product inhibition Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
glyoxylate + NAD(P)H Homo sapiens the enzyme is involved in removal of the metabolic by-product from liver glycolate + NAD(P)+
-
?
hydroxypyruvate + NAD(P)H Homo sapiens
-
D-glycerate + NAD(P)+ + H+
-
?
additional information Homo sapiens enzyme deficiency leads to primary hyperoxaluria type 2 with increased urinary oxalate levels, formation of kidney stones, and renal failure ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant enzyme Homo sapiens
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli by nickel affinity chromatography, the His-tag is cleaved by thrombin followed by gel filtration, over 95% purity Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
liver
-
Homo sapiens
-
liver the enzyme plays a critical role in the removal of the metabolic by-product glyoxylate from within the liver. Deficiency of this enzyme is the underlying cause of primary hyperoxaluria type 2 (PH2) and leads to increased urinary oxalate levels, formation of kidney stones and renal failure Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
glyoxylate + NAD(P)H
-
Homo sapiens glycolate + NAD(P)+
-
?
glyoxylate + NAD(P)H the enzyme is involved in removal of the metabolic by-product from liver Homo sapiens glycolate + NAD(P)+
-
?
hydroxypyruvate + NAD(P)H
-
Homo sapiens D-glycerate + NAD(P)+ + H+
-
?
additional information enzyme deficiency leads to primary hyperoxaluria type 2 with increased urinary oxalate levels, formation of kidney stones, and renal failure Homo sapiens ?
-
?
additional information structural basis of enzyme substrate specificity, active site structure and substrate binding, no activity with pyruvate, overview Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
D-2-hydroxy-acid dehydrogenase
-
Homo sapiens
glyoxylate reductase/hydroxypyruvate reductase
-
Homo sapiens
GRHPR
-
Homo sapiens
More the enzyme shows bifunctionality also performing the reaction of hydroxypyruvate reductase, EC 1.1.1.81 Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NADH
-
Homo sapiens
NADPH
-
Homo sapiens
NADPH binding structure Homo sapiens