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discounted EARLY registration ends Dec 31, 2014
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MetaCyc Enzyme: L-asparaginase

Gene: ansB1 Accession Number: G-9938 (MetaCyc)

Species: Pectobacterium carotovorum

Subunit composition of L-asparaginase = [AnsB1]4
         L-asparaginase subunit = AnsB1

Summary:
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 [Zhang95]. 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]).

Recombinant L-asparaginase from Pectobacterium carotovorum (previously known as Erwinia carotovora) has been expressed in Escherichia coli and purified [Kotzia05].

Map Position: [1,248,508 -> 1,249,548]

Molecular Weight of Polypeptide: 36.552 kD (from nucleotide sequence)

Unification Links: Entrez-gene:2884179 , Pride:Q6Q4F4 , Protein Model Portal:Q6Q4F4 , SMR:Q6Q4F4 , String:218491.ECA1102 , UniProt:Q6Q4F4

Relationship Links: InterPro:IN-FAMILY:IPR004550 , InterPro:IN-FAMILY:IPR006034 , InterPro:IN-FAMILY:IPR020827 , InterPro:IN-FAMILY:IPR027473 , InterPro:IN-FAMILY:IPR027474 , InterPro:IN-FAMILY:IPR027475 , Panther:IN-FAMILY:PTHR11707 , PDB:Structure:1ZCF , PDB:Structure:2GVN , PDB:Structure:2JK0 , Pfam:IN-FAMILY:PF00710 , Prints:IN-FAMILY:PR00139 , Prosite:IN-FAMILY:PS00144 , Prosite:IN-FAMILY:PS00917 , Smart:IN-FAMILY:SM00870

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.

Alternative Substrates for L-asparagine: Nα-acetyl-L-asparagine [Kotzia05 ] , succinamate [Kotzia05 ] , D-asparagine [Kotzia05 ] , L-glutamine [Kotzia05 ]

In Pathways: asparagine degradation I

Summary:
The Km values for L-asparagine and L-glutamine for recombinant L-asparaginase from Pectobacterium carotovorum (Erwinia carotovora) were 85 μM and 6800 μM, respectively [Kotzia05]. The enzyme did not hydrolyze β-alanine amide, or the dipeptide Nβ-L-aspartyl-phenylalanine methyl ester.

Kinetic Parameters:

Substrate
Km (μM)
Citations
L-asparagine
85.0
[Kotzia05]


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

Howard72: Howard JB, Carpenter FH (1972). "L-asparaginase from Erwinia carotovora. Substrate specificity and enzymatic properties." J Biol Chem 247(4);1020-30. PMID: 5010061

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

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

Zhang95: 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 Sat Dec 20, 2014, BIOCYC13A.