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MetaCyc Enzyme: L-asparaginase

Species: Thermus thermophilus

Subunit composition of L-asparaginase = [L-asparaginase subunit]6

Summary:
The relative molecular mass of native L-asparaginase from Thermus thermophilus was determined by gel filtration chromatography [Pritsa01].

L-Asparaginase has been characterized from diverse sources, including bacteria, archaea [Yao05], fungi [Sinclair94, Kil95, Raha90], and ciliates [Tsavdaridis94]. It has also been characterized from the liver and serum of guinea pigs [Zhang95a]. The enzyme has anti-tumor activity and purified L-asparaginase from Escherichia coli and Erwinia chrysanthemi have been used clinically to treat lymphoblastic leukemia and lymphosarcoma (in [Kotzia05]). The enzyme from some species contains glutaminase activity, believed to cause clinical side-effects. Enzyme preparations from species with decreased glutaminase activity, such as Pectobacterium carotovorum (previously known as Erwinia carotovora) have been characterized as potential therapeutics [Kotzia05].

L-asparaginases are L-amidohydrolases, assigned to two classes based on substrate specificity: those that primarily hydrolyze L-asparagine; and those that hydrolyze L-glutamine and L-asparagine with equal efficiency (in [Aghaiypour01]).

It has been reported that all bacterial L-asparaginases are homotetramers (in [Aghaiypour01] and in [Kotzia05]), although the enzyme from Thermus thermophilus was reported to be a homohexamer [Pritsa01]. Crystal structures have been solved for at least five bacterial L-asparaginases (in [Aghaiypour01a]). The reaction mechanism has been described as a two-step ping-pong mechanism (in [Aghaiypour01]).

The antitumor activity of Thermus thermophilus L-asparaginase has been investigated. The enzyme did not show glutaminase activity [Pritsa01a].
The relative molecular mass of the L-asparaginase subunit was determined by SDS-PAGE [Pritsa01].

Molecular Weight of Polypeptide: 33 kD (experimental) [Pritsa01 ]

Molecular Weight of Multimer: 200 kD (experimental) [Pritsa01]

pI: 6.0 [Pritsa01]

Gene-Reaction Schematic: ?

Credits:
Created 03-Mar-2007 by Fulcher CA , SRI International


Enzymatic reaction of: L-asparaginase

EC Number: 3.5.1.1

L-asparagine + H2O <=> L-aspartate + ammonium

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: asparagine degradation I

Summary:
This thermostable enzyme from Thermus thermophilus did not show glutaminase activity [Pritsa01].

Inhibitors (Competitive): L-aspartate [Pritsa01] , D-asparagine [Pritsa01]

Kinetic Parameters:

Substrate
Km (μM)
Citations
L-asparagine
2800.0
[Pritsa01]

pH(opt): 9.2 [Pritsa01]


References

Aghaiypour01: Aghaiypour K, Wlodawer A, Lubkowski J (2001). "Structural basis for the activity and substrate specificity of Erwinia chrysanthemi L-asparaginase." Biochemistry 40(19);5655-64. PMID: 11341830

Aghaiypour01a: Aghaiypour K, Wlodawer A, Lubkowski J (2001). "Do bacterial L-asparaginases utilize a catalytic triad Thr-Tyr-Glu?." Biochim Biophys Acta 1550(2);117-28. PMID: 11755201

Kil95: Kil JO, Kim GN, Park I (1995). "Extraction of extracellular L-asparaginase from Candida utilis." Biosci Biotechnol Biochem 59(4);749-50. PMID: 7772845

Kotzia05: Kotzia GA, Labrou NE (2005). "Cloning, expression and characterisation of Erwinia carotovora L-asparaginase." J Biotechnol 119(4);309-23. PMID: 15951039

Pritsa01: Pritsa AA, Kyriakidis DA (2001). "L-asparaginase of Thermus thermophilus: purification, properties and identification of essential amino acids for its catalytic activity." Mol Cell Biochem 216(1-2);93-101. PMID: 11216870

Pritsa01a: Pritsa AA, Papazisis KT, Kortsaris AH, Geromichalos GD, Kyriakidis (2001). "Antitumor activity of L-asparaginase from Thermus thermophilus." Anticancer Drugs 12(2);137-42. PMID: 11261887

Raha90: Raha SK, Roy SK, Dey SK, Chakrabarty SL (1990). "Purification and properties of an L-asparaginase from Cylindrocarpon obtusisporum MB-10." Biochem Int 21(6);987-1000. PMID: 2080924

Sinclair94: Sinclair K, Warner JP, Bonthron DT (1994). "The ASP1 gene of Saccharomyces cerevisiae, encoding the intracellular isozyme of L-asparaginase." Gene 144(1);37-43. PMID: 8026756

Tsavdaridis94: Tsavdaridis IK, Triantafillidou DC, Kyriakidis DA (1994). "Two forms of L-asparaginase in Tetrahymena thermophila." Biochem Mol Biol Int 32(1);67-77. PMID: 8012291

Yao05: Yao M, Yasutake Y, Morita H, Tanaka I (2005). "Structure of the type I L-asparaginase from the hyperthermophilic archaeon Pyrococcus horikoshii at 2.16 angstroms resolution." Acta Crystallogr D Biol Crystallogr 61(Pt 3);294-301. PMID: 15735339

Zhang95a: Zhang N, Clarke F, Di Trapani G, Keough D, Beacham I (1995). "Guinea pig serum L-asparaginase: purification, and immunological relationship to liver L-asparaginase and serum L-asparaginases in other mammals." Comp Biochem Physiol B Biochem Mol Biol 112(4);607-12. PMID: 8590375


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Fri Dec 19, 2014, BIOCYC14A.