Asparaginases (amidohydrolases, E.C. 3.5.1.1) are enzymes that catalyze the hydrolysis of asparagine to aspartic acid and ammonia. In bacteria, there are two classes of amidohydrolases. This model represents type II L-asparaginases, which tend to be highly specific for asparagine and localized to the periplasm. They are potent antileukemic agents and have been used in the treatment of acute lymphoblastic leukemia (ALL), but not without severe side effects. Tumor cells appear to have a heightened dependence on exogenous L-aspartate, and depleting their surroundings of L-aspartate may starve cancerous ALL cells. Type II L-asparaginase acts as a tetramer, which is actually a dimer of two tightly bound dimers. A conserved threonine residue is thought to supply the nucleophile hydroxy-group that attacks the amide bond. Many bacterial L-asparaginases have both L-asparagine and L-glutamine hydrolysis activities, to a different degree, and some of them are annotated as asparaginase/glutaminase.
Comment:Type II L-asparaginases are active as homotetramers. Two intimate dimers each provide two active sites; the N-terminal domain of one subunit and the C-terminal domain of the second subunit appear to each contribute residues to each active site.
Structure:1DJP: Pseudomonas glutaminase-asparaginase dimer binds inhibitor in one of two active sites of the dimer
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