Asparaginase

Function

L-Asparaginases are enzymes that hydrolyze the amide group of the amino acid L-asparagine (L-Asn) to L-aspartate, with the simultaneous release of ammonia. They are often referred to as ASNase and assigned the EC number 3.5.1.1; if significant glutaminase co-activity (hydrolysis of the similar amino acid L-glutamine) is also present, the EC number is 3.5.1.38. Some ASNases that belong to other classes (see below) are assigned EC 3.4.19.5. (GASP) plays an imortant role in asparagine-linked glycoprotein degradation^[1].

Relevance

Beyond pure academic curiosity, ASNases are also studied because of their potential application as first-line drugs for the treatment of acute lymphoblastic leukemia (ALL) [1-4]^[2][3]. By clearing L-asparagine from circulation, they starve the L-Asn-dependent malignant cells to death, while sparing the L-Asn-independent healthy cells. The first L-asparaginase introduced for clinical treatment of ALL was Elspar (EcAII from E. coli), followed by Erwinase (ErA from E. chrysanthemi). ASNases are also used in food industry to prevent the formation of acrylamide from L-Asn in fried starch foods [5, 6]. ^[4].

Disease

GASP mutants cause the autosomal recessive lysosomal storage disease aspartylglycosaminuria^[5].

Structural highlights

.^[6] Ligands asparagine (in white) and aspartic acid (in salmon) are shown in spacefill representation.

• , chain A. Water molecules shown as red spheres.
• , chain A.
• .

3D structures of asparaginase

Asparaginase 3D structures