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Enzyme Nomenclature
Information on EC 3.5.2.9 - 5-oxoprolinase (ATP-hydrolysing)
Word Map on EC 3.5.2.9
- 3.5.2.9
-
gamma-glutamyl
- 5-oxoproline
-
5-oxoprolinuria
- l-glutamate
- l-2-oxothiazolidine-4-carboxylate
- medicine
-
cyclotransferase
-
acidurias
-
decyclization
-
gamma-glutamyl-cysteine
- gamma-glutamylcyclotransferase
-
meister
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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
topEC NUMBER 
COMMENTARY 
3.5.2.9
-
RECOMMENDED NAME
GeneOntology No.
5-oxoprolinase (ATP-hydrolysing)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + 5-oxo-L-proline + 2 H2O = ADP + phosphate + L-glutamate
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
carboxylic acid amide hydrolysis
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
SYSTEMATIC NAME
IUBMB Comments
5-oxo-L-proline amidohydrolase (ATP-hydrolysing)
-
CAS REGISTRY NUMBER
COMMENTARY
9075-46-1
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
-
the enzyme is involved in the gamma-glutamyl cycle, a six-enzyme cycle that represents the primary pathway for glutathione synthesis and degradation
physiological function
comparison of the growth of 5-oxoprolinase deletion strains with wild-type strains in a variety of growth conditions does not yield any discernible phenotypes. Cells of glutamate auxotroph aco1D strain expressing OXP1 are able to grow on 5-oxoproline, although the growth is very slow
malfunction
-
inherited 5-oxoprolinase deficiency is a rare 5-oxoprolinase deficiency is an extremely rare disorder of the gamma-glutamyl cycle characterised by 5-oxoprolinuria, heterogeneity of the clinical presentation which ranges from normal to significant neurological involvement, genotype-phenotype correlation, phenotypes, overview
malfunction
-
inherited 5-oxoprolinase deficiency is a rare inborn condition characterised by 5-oxoprolinuria. Three enzyme mutations are involved: p.H870Pfs in a homozygous state, which results in a truncated protein, and two heterozygous missense changes, S323R and V1089I
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-imidazoline-4-carboxylate + ATP + H2O
2-imidazoline-4-carboxylate + ADP + phosphate
-
does not undergo ring cleavage, but stimulates formation of inorganic phosphate from ATP
-
-
?
5-oxo-L-proline + ATP + 2 H2O
L-glutamate + phosphate + ADP
-
assay at pH 7.2, 5 mM substrate, 4°C, 20 min
-
-
?
5-oxo-L-proline + ATP + H2O
L-glutamate + ADP + phosphate
assay at 30°C, pH 9.5, reaction stopped by 20 microl acetic acid and heating for 5 min at 100°C
-
-
?
DL-cis-2-oxo-5-methyloxazolidine-4-carboxylate + H2O
DL-threonine + ADP + phosphate
-
-
-
-
?
L-2-oxooxazolidine-4-carboxylate + H2O + ATP
L-serine + ADP + phosphate
-
-
-
-
?
L-dihydroorotate + H2O
?
-
do not undergo ring cleavage, but stimulates formation of inorganic phosphate from ATP
-
-
?
L-trans-2-oxo-5-methyloxazolidine-4-carboxylate + H2O
L-threonine + ADP + phosphate
-
-
-
-
?
2-imidazolidone-4-carboxylate + ATP + H2O
2-imidazolidone + ADP + phosphate
-
-
-
-
?
2-imidazolidone-4-carboxylate + ATP + H2O
2-imidazolidone + ADP + phosphate
-
promotes enzymatic hydrolysis of ATP but is not itself hydrolyzed
-
-
?
2-piperidone-6-carboxylate + ATP + H2O
2-aminoadipate + phosphate + ADP
-
-
-
-
?
2-piperidone-6-carboxylate + ATP + H2O
2-aminoadipate + phosphate + ADP
-
-
-
?
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
?
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
?
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
?
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
?
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
component F8 + component beta5
-
-
?
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
?
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
209370, 209371, 209373, 209374, 209375, 209376, 209377, 209378, 209379, 209380, 209381, 209382, 209383, 209384, 209385, 209386, 209387
-
-
-
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
-
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
conversion essentially irreversible, very slow reversal can be shown by measurement of ATP formation in presence of high glutamate concentrations
-
-
-
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
conversion essentially irreversible, very slow reversal can be shown by measurement of ATP formation in presence of high glutamate concentrations
-
-
ir
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
-
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
-
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
ATP is required
-
-
?
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
?
L-2-oxothiazolidine-4-carboxylate + H2O + ATP
L-cysteine + ADP + phosphate
-
-
-
-
?
L-2-oxothiazolidine-4-carboxylate + H2O + ATP
L-cysteine + ADP + phosphate
-
-
-
-
?
L-2-oxothiazolidine-4-carboxylate + H2O + ATP
L-cysteine + ADP + phosphate
-
-
-
-
?
L-2-oxothiazolidine-4-carboxylate + H2O + ATP
L-cysteine + ADP + phosphate
-
-
-
-
?
L-2-oxothiazolidine-4-carboxylate + H2O + ATP
L-cysteine + ADP + phosphate
-
-
-
-
?
L-2-oxothiazolidine-4-carboxylate + H2O + ATP
L-cysteine + ADP + phosphate
-
-
-
-
?
L-2-oxothiazolidine-4-carboxylate + H2O + ATP
L-cysteine + ADP + phosphate
-
-
-
-
?
additional information
?
-
-
CTP, TTP and UTP are no substrates
-
-
-
additional information
?
-
-
no activity observed with 5-oxo-D-proline
-
-
-
additional information
?
-
-
no activity observed with 5-oxo-D-proline
-
-
-
additional information
?
-
-
no activity observed with 5-oxo-D-proline
-
-
-
additional information
?
-
-
5-oxo-D-proline, 2-pyrrolidone-4-carboxylate, N-methyl-5-oxo-L-proline and N-acetyl-L-alanine are no substrates
-
-
-
additional information
?
-
-
L-proline, 2-pyrrolidone, N-methyl-5-oxo-L-proline, DL-piperidine-2-carboxylic acid and cyclohexanone-3-carboxylic acid are no substrates
-
-
-
additional information
?
-
-
L-proline, 2-pyrrolidone, N-methyl-5-oxo-L-proline, DL-piperidine-2-carboxylic acid and cyclohexanone-3-carboxylic acid are no substrates
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
?
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
?
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
?
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
?
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
?
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
209370, 209373, 209375, 209376, 209378, 209379, 209380, 209381, 209382, 209383, 209384, 209385, 209386, 209387
-
-
-
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
-
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
conversion essentially irreversible, very slow reversal can be shown by measurement of ATP formation in presence of high glutamate concentrations
-
-
-
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
conversion essentially irreversible, very slow reversal can be shown by measurement of ATP formation in presence of high glutamate concentrations
-
-
ir
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
-
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
-
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K+
Mg2+
Mn2+
additional information
additional information
enzyme requires ATP, a monovalent cation such as K+ or NH4+ and a divalent cation such as Mg2+ or Mn2+
additional information
-
enzyme requires ATP, a monovalent cation such as K+ or NH4+ and a divalent cation such as Mg2+ or Mn2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
DL-cis-2-oxo-5-methyloxazolidine-4-carboxylate
-
inhibition of IPTase activity
L-trans-2-oxo-5-methyloxazolidine-4-carboxylate
-
inhibition of glutamate formation; inhibition of IPTase activity
-
L-2-imidazolidone-4-carboxylate
-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-imidazolidone-4-carboxylate
-
5-oxoproline analog, stimulates rapid ATP cleavage, but is not hydrolyzed itself
L-glutamine
-
enhanced enzyme activity in jejunal mucosa of tumor-bearing rats
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.625
after purification by Sepharyl S-300, Blue Sepharose and Phenyl Sepharose column chromatography
3
-
measured in jejunal mucosa after treatment with dietary glutamine in DMBA-treated rats without tumor
4.17
-
measured in jejunal mucosa after treatment with dietary glutamine in normal rats
4.33
-
measured in jejunal mucosa after treatment with dietary glutamine in DMBA-treated rats with tumor
75
243
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.8 - 8
8.2
9.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
325000
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
polymer
polymer
-
2 protein compounds, component A exhibits 5-oxo-L-proline depedent ATPase activity, component A composed of 6 heterodimers, 6 * 51000 + 6 * 64000, SDS-PAGE, component B is a coupling protein without ATPase activity, 8 * 82000, octamer, SDS-PAGE
polymer
-
component A 1 * 65500 + 1 * 50000, component B 1 * 80000, SDS-PAGE
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5 - 8.5
-
most stable at pH 7.5, loses activity rapidly below pH 5.5 and above pH 9
209394
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50
-
64% initial activity retained at 60°C, loses all initial activity at 70°C
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
unstable in absence of 5-oxo-L-proline
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, 30 mM Tris-HCl buffer pH 7.8, 10 mM potassium chloride, 1 mM MgCl2, 5 mM 5-oxoproline, activity decreases to about 60% of its initial value after 2 days, 42% after 4 days and 40% after 5-6 days, addition of dithiothreitol leads to 104% of initial activity
-
4°C, loses progressively activity, 60% initial activity lost in 6 days, activity completely restored upon addition of 5 mM dithiothreitol
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Sepharyl S-300 gel filtration, Blue Sepharose and Phenyl Sepharose column chromatography
-
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
amino acid sequence determined by cDNA cloning, gene expressed in Escherichia coli
cDNA in pT7-7, subcloned into mammalian expression vector pRc/CMV, transfected into MCF7
-
expression in Saccharamyces cerevisiae, N-terminally His-tagged
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
V1089I
-
naturally occuring mutation, not involved into 5-oxoprolinase deficiency
additional information
additional information
oxp1-1 and oxp1-2, oxoprolinase knockout mutants
additional information
-
in a yeast in vivo growth assay mutations S323R, G860R, and D1241V affect the activity of the enzyme
additional information
subunit consists of two distinct domains HyuA and HyuB. Cells of a met15 deletion strain expressing either the HyuA or the HyuB domains alone cannot utilize 5-oxoproline sulfur analogue OTC as sole source of sulfur. Cells coexpressing both HyuA and HyuB domains are able to grow on OTC as a sole source of sulfur, similar to cells expressing full-length yeast 5-oxoprolinase gene
additional information
-
subunit consists of two distinct domains HyuA and HyuB. Cells of a met15 deletion strain expressing either the HyuA or the HyuB domains alone cannot utilize 5-oxoproline sulfur analogue OTC as sole source of sulfur. Cells coexpressing both HyuA and HyuB domains are able to grow on OTC as a sole source of sulfur, similar to cells expressing full-length yeast 5-oxoprolinase gene
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
animal model for the human condition 5-oxoprolinuria, an inborn deficiency of renal 5-oxoprolinase activity
medicine
-
animal model for the human condition 5-oxoprolinuria, an inborn deficiency of renal 5-oxoprolinase activity; potenial implications for carcinogenesis and cancer chemotherapy
medicine
-
animal model for the human condition 5-oxoprolinuria, an inborn deficiency of renal 5-oxoprolinase activity
medicine
-
clinical applications, substrate 5-oxo-L-proline sensitizes tumors to the alkylating agent melphalan
medicine
-
5-oxoprolinuria is primarily associated with inborn errors of the gamma-glutamyl cycle
medicine
-
occurrence of a futile cycle in patients with cystinosis. The enzyme gamma-glutamyl cysteine synthetase, in the absence of cysteine, forms 5-oxoproline instead of the normal substrate, gamma-glutamyl cysteine, and the 5-oxoproline is converted into glutamate by the ATP-dependant enzyme, 5-oxoprolinase. In cysteine-limiting conditions, glutamate is cycled back into glutamate via 5-oxoproline at the cost of two ATP molecules without production of glutathione and is the cause of the decreased levels of glutathione synthesis, as well as the ATP depletion observed in these cells
medicine
-
animal model for the human condition 5-oxoprolinuria, an inborn deficiency of renal 5-oxoprolinase activity
-
LINKS TO OTHER DATABASES (specific for EC-Number 3.5.2.9)
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