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Information on EC 3.5.2.9 - 5-oxoprolinase (ATP-hydrolysing) and Organism(s) Homo sapiens and UniProt Accession O14841
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3.5.2.9 5-oxoprolinase (ATP-hydrolysing)Specify your search results
Word Map
- 3.5.2.9
- 5-oxoproline
-
gamma-glutamyl
-
5-oxoprolinuria
- l-2-oxothiazolidine-4-carboxylate
- medicine
-
cyclotransferase
-
decyclization
-
gamma-glutamyl-cysteine
-
atp-hydrolyzing
-
meister
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
5-oxoprolinase, 5-opase, oplah, 5-oxo-l-prolinase, opase, oxoprolinase, fgoxp1, fgoxp2, atp-dependent 5-oxoprolinase, prokaryotic 5-oxoprolinase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
5-OPase
-
-
-
-
5-oxo-L-prolinase
-
-
-
-
5-oxoprolinase
-
-
-
-
L-pyroglutamate hydrolase
-
-
-
-
oxoprolinase
-
-
-
-
pyroglutamase
-
-
-
-
pyroglutamase (ATP-hydrolysing)
-
-
-
-
pyroglutamate hydrolase
-
-
-
-
pyroglutamic hydrolase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
carboxylic acid amide hydrolysis
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
5-oxo-L-proline amidohydrolase (ATP-hydrolysing)
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CAS REGISTRY NUMBER
COMMENTARY
9075-46-1
-
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
5-oxo-L-proline + H2O + ATP
L-glutamate + ADP + phosphate
-
-
-
-
?
L-2-oxothiazolidine-4-carboxylate + H2O + ATP
L-cysteine + ADP + phosphate
-
-
-
-
?
NATURAL SUBSTRATE
NATURAL 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
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
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
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). OPLA_HUMAN
1288
0
137457
Swiss-Prot
other Location (Reliability: 3)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
V1089I
naturally occuring mutation, not involved into 5-oxoprolinase deficiency
additional information
additional information
in a yeast in vivo growth assay mutations S323R, G860R, and D1241V affect the activity of the enzyme
additional information
-
in a yeast in vivo growth assay mutations S323R, G860R, and D1241V affect the activity of the enzyme
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cDNA in pT7-7, subcloned into mammalian expression vector pRc/CMV, transfected into MCF7
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
clinical applications, substrate 5-oxo-L-proline sensitizes tumors to the alkylating agent melphalan
medicine
-
animal model for the human condition 5-oxoprolinuria, an inborn deficiency of renal 5-oxoprolinase activity
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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Van Der Werf, P.; Stephani, R.A.; Meister, A.
Accumulation of 5-oxoproline in mouse tissues after inhibition of 5-oxoprolinase and administration of amino acids: Evidence for function of the gamma-glutamyl cycle
Proc. Natl. Acad. Sci. USA
71
1026-1029
1974
Homo sapiens, Mus musculus, Pseudomonas sp., Rattus norvegicus
Van Der Werf, P.; Stephani, R.A.; Orlowski, M.; Meister, A.
Inhibition of 5-oxoprolinase by 2-imidazolidone-4-carboxylic acid
Proc. Natl. Acad. Sci. USA
70
759-761
1973
Homo sapiens, Mus musculus, Rattus norvegicus, Rattus norvegicus Sprague-Dawley
Van Der Werf, P.; Orlowski, M.; Meister, A.
Enzymatic conversion of 5-oxo-L-proline (L-pyrrolidone carboxylate) to L-glutamate coupled with cleavage of adenosine triphosphate to adenosine diphosphate, a reaction in the gamma-glutamyl cycle
Proc. Natl. Acad. Sci. USA
68
2982-2985
1971
Ovis aries, Homo sapiens, Rattus norvegicus, Sus scrofa
Srivenugopal, K.S.; Ali-Osman, F.
Activity and distribution of the cysteine prodrug activating enzyme, 5-oxo-L-prolinase, in human normal and tumor tissues
Cancer Lett.
117
105-111
1997
Homo sapiens
Chen, X.; Schecter, R.L.; Griffith, O.W.; Hayward, M.A.; Alpert, L.C.; Batist, G.
Characterization of 5-oxo-L-prolinase in normal and tumor tissues of humans and rats: A potential new target for biochemical modulation of glutathione
Clin. Cancer Res.
4
131-138
1998
Homo sapiens, Rattus norvegicus
Chen, X.; Batist, G.
Sensitization effect of L-2-oxothiazolidine-4-carboxylate on tumor cells to melphalan and the role of 5-oxo-L-prolinase in glutathione modulation in tumor cells
Biochem. Pharmacol.
56
743-749
1998
Homo sapiens
Ruijter, G.J.; Mourad-Baars, P.E.; Ristoff, E.; Onkenhout, W.; Poorthuis, B.J.
Persistent 5-oxoprolinuria with normal glutathione synthase and 5-oxoprolinase activities
J. Inherit. Metab. Dis.
29
587
2006
Homo sapiens
Kumar, A.; Bachhawat, A.K.
A futile cycle, formed between two ATP-dependant gamma-glutamyl cycle enzymes, gamma-glutamyl cysteine synthetase and 5-oxoprolinase: the cause of cellular ATP depletion in nephrotic cystinosis?
J. Biosci.
35
21-25
2010
Homo sapiens
Almaghlouth, I.; Mohamed, J.; Al-Amoudi, M.; Al-Ahaidib, L.; Al-Odaib, A.; Alkuraya, F.
5-Oxoprolinase deficiency: report of the first human OPLAH mutation
Clin. Genet.
82
193-196
2012
Homo sapiens (O14841), Homo sapiens
Calpena, E.; Deshpande, A.A.; Yap, S.; Kumar, A.; Manning, N.J.; Bachhawat, A.K.; Espinos, C.
New insights into the genetics of 5-oxoprolinase deficiency and further evidence that it is a benign biochemical condition
Eur. J. Pediatr.
174
407-411
2015
Homo sapiens (O14841), Homo sapiens
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