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Information on EC 1.7.3.3 - factor-independent urate hydroxylase and Organism(s) Cyberlindnera jadinii and UniProt Accession P78609
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1.7.3.3 factor-independent urate hydroxylaseIUBMB Comments
This enzyme was previously thought to be a copper protein, but it is now known that the enzymes from soy bean (Glycine max), the mould Aspergillus flavus and Bacillus subtilis contains no copper nor any other transition-metal ion. The 5-hydroxyisourate formed decomposes spontaneously to form allantoin and CO2, although there is an enzyme-catalysed pathway in which EC 3.5.2.17, hydroxyisourate hydrolase, catalyses the first step. The enzyme is different from EC 1.14.13.113 (FAD-dependent urate hydroxylase).
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Word Map
- 1.7.3.3
- hyperuricemia
- peroxisomal
- xanthine
- allopurinol
- gout
- purine
- catalase
- allantoin
-
biosensors
-
electrode
-
hematologic
- creatinine
-
oxonic
- febuxostat
- allantoinase
- hyperkalemia
- hypoxanthine
-
prophylaxis
- flavus
- hyperphosphatemia
-
urate-lowering
-
ureide
- methemoglobinemia
-
pegylated
-
amperometric
-
uricosuric
-
hypocalcemia
-
tophi
- benzbromarone
-
hominoid
-
phosphotungstate
- microbodies
-
hypouricemic
- probenecid
- utilis
- pimecrolimus
- pharmacology
- medicine
- analysis
- synthesis
-
weight-based
-
nodule-specific
-
miocene
- drug development
The taxonomic range for the selected organisms is: Cyberlindnera jadinii
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
uricase, rasburicase, urate oxidase, uricase ii, uric acid oxidase, uricozyme, aguox, nodulin 35, elitek, fasturtec, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
N-35
-
-
-
-
Nodule specific uricase
-
-
-
-
Nodulin 35
-
-
-
-
Nodulin 35 homolog
-
-
-
-
Non-symbiotic uricase
-
-
-
-
oxidase, urate
-
-
-
-
Urate oxidase
uric acid oxidase
-
-
-
-
uricase
Urate oxidase
-
-
-
-
uricase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
reduction
-
-
-
-
oxidation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-
SYSTEMATIC NAME
IUBMB Comments
urate:oxygen oxidoreductase
This enzyme was previously thought to be a copper protein, but it is now known that the enzymes from soy bean (Glycine max), the mould Aspergillus flavus and Bacillus subtilis contains no copper nor any other transition-metal ion. The 5-hydroxyisourate formed decomposes spontaneously to form allantoin and CO2, although there is an enzyme-catalysed pathway in which EC 3.5.2.17, hydroxyisourate hydrolase, catalyses the first step. The enzyme is different from EC 1.14.13.113 (FAD-dependent urate hydroxylase).
CAS REGISTRY NUMBER
COMMENTARY
9002-12-4
-
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
urate + O2 + H2O
5-hydroxyisourate + H2O2
-
-
-
-
?
uric acid + O2 + H2O
5-hydroxyisourate + H2O2
-
purine degradation
-
-
?
additional information
?
-
-
enzyme catalyzes the oxidation of uric acid to a more soluble and easily excreted compound, allantoin
-
-
?
additional information
?
-
-
purine degradation, urate oxidase catalyzes the oxidation of uric acid with poor solubility to produce 5-hydroxyisourate and allantoin
-
-
?
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
urate + O2 + H2O
5-hydroxyisourate + H2O2
-
-
-
-
?
uric acid + O2 + H2O
5-hydroxyisourate + H2O2
-
purine degradation
-
-
?
additional information
?
-
-
enzyme catalyzes the oxidation of uric acid to a more soluble and easily excreted compound, allantoin
-
-
?
additional information
?
-
-
purine degradation, urate oxidase catalyzes the oxidation of uric acid with poor solubility to produce 5-hydroxyisourate and allantoin
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
copper
Iron
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
beta-mercaptoethanol
-
about 60% residual activity after 1 h incubation with 0.5 mM beta-mercaptoethanol at pH 8.5 and 25°C
D-sorbitol
-
about 70% residual activity after 1 h incubation with 0.5 mM D-sorbitol at pH 8.5 and 25°C
sodium deoxycholate
-
about 90% residual activity after 1 h incubation with 0.5 mM sodium deoxycholate at pH 8.5 and 25°C
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
2.49
-
urate oxidase including p-azido-L-phenylalanine instead of Phe at position 281, in 0.1 M borate, pH 8.4
8.26
-
urate oxidase including p-azido-L-phenylalanine instead of Phe at position 170, in 0.1 M borate, pH 8.4
additional information
additional information
-
among the parameters investigated in shaking flask cultures, the pH value of medium and inoculum size has great influence on the recombinant uricase production, the maximum extracellular uricase yield of 2.6 U/ml is obtained in shaking flask culture
additional information
-
at pH 5.5, the extracellular uricase production reaches top of 7.5 U/ml at 58 h, when fermentation is performed at pH 6.5 for 62 h, 14.5 U/ml of extracellular uricase and 23.3 U/ml of intracellular uricase are produced, the total specific uricase production at pH 6.5 is 1.7times of that at pH 5.5
additional information
-
in high density fermentation in YPG medium at 37°C, extracellular uricase activity increases significantly during the first 40 h, highest extracellular uricase level of 52.3 U/ml is obtained after 58 h of induction, as well as the intracellular activity of 60.3 U/ml, after 86 h of fermentation and 58 h of induction, a total uricase activity of 112600 U/l is obtained, the extracellular and intracellular yields of uricase in high cell density fermentation increased by 3.7fold and 3.5fold compared with the batch fermentation
additional information
-
the combined use of fed-batch culture and pH-controlled strategy increases the expression level of uricase significantly, the extracellular uricase production of 52.3 U/ml (approximately 2.1 g/l of protein) is obtained, which is much higher than that produced by recombinant Escherichia coli strains
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5
-
yield of recombinant uricase is significantly improved by the combined use of a high cell-density cultivation technique and a pH control strategy of switching culture pH from 5.5 to 6.5 in the induction phase
8.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5 - 9.5
-
free uricase shows at least 50% relative activity between pH 6.5 and 9.5, around pH 7.5, free uricase remains 81.16% of its maximum activity, while the uricase loaded in the lipid vesicles remains almost the same high activity (178.26%) as its optimum activity (179.72%)
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20 - 50
20 - 70
-
free uricase shows at least 50% relative activity between 20 and 70°C
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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). URIC_CYBJA
303
0
34195
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
to 1.93 A resolution. Space group P212121 with unit cell parameters a 69.16 A, b 139.31 A, c 256.33 A, and alpha =beta =gamma =90°
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 9.5
-
in case of uricase entrapped in lipid vesicles, the remaining activity keeps more than 90% during the pH of 7.0-9.5, and the maximum remaining activity is 98.04% at pH 8.0 when incubated at 40°C or 40 min. For the free uricase, the maximum remaining activity is 86.59% at pH 8.5 when incubated at 40°C or 40 min
712197
additional information
-
uricase activity in 50 h culture broth with pH values of 5.5 and 6.0 decreases more rapidly than that in cultures with pH values of 6.5 and 7.0, at pH 5.5, about 78% of initial uricase activity is lost within 25 h, under the same conditions, more than 85% of initial uricase activity remains in culture broth of pH 6.5 and 7.0, uricase activity in 66 h culture broth with pH 7.0 degrades much more rapidly than that in samples from 50 h culture, while for pH 6.5, the uricase is still stable, loss of uricase activity is caused by the degradation in acidic environment by proteases secreted by the host cells or releases from host cell lyses, low pH may cause instability of uricase
695795
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
55
-
uricase entrapped in lipid vesicles at enzyme concentrations of 0.005 and 0.1 mg/ml shows no loss of activity after 5 h at 55°C. Uricase entrapped in lipid vesicles at enzyme concentrations of 0.01 mg/ml shows about 35% loss of activity after 5 h at 55°C. Uricase entrapped in lipid vesicles at enzyme concentrations of 0.005 mg/ml shows about 50% loss of activity after 5 h at 55°C. The free uricase at 0.005 mg/ml is rapidly deactivated to about 30% of the initial activity within an incubation time of 2 h, while more than 70% of the initial enzyme activity remains for the uricase at 0.1 mg/ml in the identical incubation time
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
at the physiological pH, significant increase of enzyme activity is found for the uricase entrapped in the lipid vesicles (1.8times that of free uricase) at their respective optimum pH. Free uricase shows rapid decrease in its enzymatic activity with a half life of less than 20 min when incubated with trypsin. Uricase entrapped in the lipid vesicles gradually loses its activity but still 50% of the original activity remains after 60 min (remaining activity is 7.32% in case of free uricase)
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dithiothreitol prevents polymerization and stabilizes throughout purification
-
lower stability in solutions of phosphate buffer than in borate buffer
-
proteolytic digestion by endopeptidases cause rapid loss of activity, exopeptidases have slight effect
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, free uricase in borate buffer (pH 8.5), 28 days, 70% loss of activity
-
4°C, uricase in lipid vesicles in borate buffer (pH 8.5), 28 days, no loss of activity
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
developing of a method for genetically incorporating p-azido-L-phenylalanine into target protein in Escherichia coli in a site-specific manner utilizing a tyrosyl suppressor tRNA/aminoacyl-tRNA synthetase system, substitution of p-azido-L-phenylalanine for F170 or F281 in urate oxidase, optimization of the system by adding a Shine-Dalgarno sequence and tandem suppressor tRNA in order to increase the expression levels of tyrosyl suppressor tRNA and aminoacyl-tRNA synthetase
-
uricase production by the recombinant Hansenula polymorpha strain MU200 harboring Candida utilis uricase gene under the control of methanol oxidase promoter using Saccharomyces cerevisiae alpha-factor signal peptide as the secretory sequence
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
high-yield expression of uricase in Escherichia coli and establishment of an efficient three-step protein purification protocol. The purity of the recombinant protein is more than 98% and the specific activity is 38.4 IU/mg
drug development
-
urate oxidase has the potential to be a therapeutic target for the treatment of gout
medicine
medicine
-
uricase is an important medical enzyme which can be used to determine urate in clinical analysis, to therapy gout, hyperuricemia, and tumor lysis syndrome
medicine
-
oral uricase therapy significantly decreases plasma uric acid concentrations in pigs with chronic kidney disease
medicine
-
the enzyme, when engineered as bifunctional protein with uricase and peroxidase activities (constructed by direct fusion of Candida utilis uricase and Vitreoscilla hemoglobin), can be used for evaluation and measurement of uric acid from lyophilized serum
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Adamek, V.; Kralova, B.; Suchova, M.; Valentova, O.; Demnerova, K.
Purification of microbial uricase
J. Chromatogr.
497
268-275
1989
Cyberlindnera jadinii
Kralova, B.; Lehejckova, R.; Demnerova, K.; Dobransky, T.
Extraction of uricase from Candida utilis
Biotechnol. Lett.
8
99-102
1986
Cyberlindnera jadinii
-
Nishimura, H.; Yoshida, K.; Yokota, Y.; Matsushima, A.; Inada, Y.
Physicochemical properties and states of sulfhydryl groups of uricase from Candida utilis
J. Biochem.
91
41-48
1982
Cyberlindnera jadinii
Chen, R.H.L.; Abuchowski, A.; Van Es, T.; Palczuk, N.C.; Davis, F.F.
Properties of two urate oxidases modified by the covalent attachment of poly(ethylene glycol)
Biochim. Biophys. Acta
660
293-298
1981
Cyberlindnera jadinii, Sus scrofa
Itaya, K.; Fukumoto, J.; Yamamoto, T.
Studies on urate oxidase of Candida utilis. Part II. Some physical and chemical properties of the purified enzyme
Agric. Biol. Chem.
35
813-821
1971
Cyberlindnera jadinii
-
Fitzpatrick, D.A.; McGeeney, K.F.
Resistance of urate oxidase to proteolytic digestion
Biochem. Soc. Trans.
3
1253-1255
1975
Aspergillus flavus, Metabacillus fastidiosus, Cyberlindnera jadinii
-
Itaya, K.; Yamamoto, T.; Fukumoto, J.
Studies on yeast uricase. Part I. Purification and some enzymatic properties of yeast uricase
Agric. Biol. Chem.
31
1256-1264
1967
Cyberlindnera jadinii
-
Chen, Z.; Wang, Z.; He, X.; Guo, X.; Li, W.; Zhang, B.
Uricase production by a recombinant Hansenula polymorpha strain harboring Candida utilis uricase gene
Appl. Microbiol. Biotechnol.
79
545-554
2008
Cyberlindnera jadinii
Chen, M.; Cai, L.; Fang, Z.; Tian, H.; Gao, X.; Yao, W.
Site-specific incorporation of unnatural amino acids into urate oxidase in Escherichia coli
Protein Sci.
17
1827-1833
2008
Cyberlindnera jadinii
Tan, Q.Y.; Wang, N.; Yang, H.; Zhang, L.K.; Liu, S.; Chen, L.; Liu, J.; Zhang, L.; Hu, N.N.; Zhao, C.J.; Zhang, J.Q.
Characterization, stabilization and activity of uricase loaded in lipid vesicles
Int. J. Pharm.
384
165-172
2010
Cyberlindnera jadinii
Liu, X.; Wen, M.; Li, J.; Zhai, F.; Ruan, J.; Zhang, L.; Li, S.
High-yield expression, purification, characterization, and structure determination of tag-free Candida utilis uricase
Appl. Microbiol. Biotechnol.
92
529-537
2011
Cyberlindnera jadinii (P78609), Cyberlindnera jadinii
Phuadraksa, T.; Chittrakanwong, J.; Tullayaprayouch, K.; Onsirisakul, N.; Wichit, S.; Yainoy, S.
Engineering of bifunctional enzymes with uricase and peroxidase activities for simple and rapid quantification of uric acid in biological samples
Catalysts
10
428
2020
Cyberlindnera jadinii
-
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