Asparaginase

From Proteopedia

E. coli asparaginase I tetramer complex with aspartic acid, asparagine, ethylene glycol and Cl- ions (green), 2p2n Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Relevance 3 Disease 4 Structural highlights 5 3D structures of asparaginase Function Asparaginase (ASP) catalyzes the conversion of asparagine to aspartic acid (AA). The ALL cells require high concentrations of asparagine which becomes scarce when high doses of ASP are present. Isoaspartyl peptidase/L-asparaginase (IPA) has activity of L-asparaginase and of β-aspartyl peptidase[1]. Glycosylasparaginase (GASP) plays an imortant role in asparagine-linked glycoprotein degradation[2]. Relevance ASP I is used in the food processing industry to reduce the formation of the carcinogen acrylamide in the production of starchy food products[3]. A different kind of ASP – ASP II – is used as drug (Elspar) in the treatment of cancer such as acute lymphoblastic leukemia (ALL)[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

References

1. ↑ Prahl A, Pazgier M, Hejazi M, Lockau W, Lubkowski J. Structure of the isoaspartyl peptidase with L-asparaginase activity from Escherichia coli. Acta Crystallogr D Biol Crystallogr. 2004 Jun;60(Pt 6):1173-6. Epub 2004, May 21. PMID:15159592 doi:10.1107/S0907444904003403
2. ↑ Wang Y, Guo HC. Crystallographic snapshot of a productive glycosylasparaginase-substrate complex. J Mol Biol. 2007 Feb 9;366(1):82-92. Epub 2006 Sep 26. PMID:17157318 doi:10.1016/j.jmb.2006.09.051
3. ↑ Xu F, Oruna-Concha MJ, Elmore JS. The use of asparaginase to reduce acrylamide levels in cooked food. Food Chem. 2016 Nov 1;210:163-71. doi: 10.1016/j.foodchem.2016.04.105. Epub 2016 , Apr 22. PMID:27211635 doi:http://dx.doi.org/10.1016/j.foodchem.2016.04.105
4. ↑ Kwok CS, Kham SK, Ariffin H, Lin HP, Quah TC, Yeoh AE. Escherichia coli-asparaginase (Elspar) is superior to Erwinia-asparaginase (Erwinase) in childhood acute lymphoblastic leukaemia (ALL) induction--an early response study using minimal residual disease (MRD) markers. Ann Acad Med Singapore. 2004 Sep;33(5 Suppl):S45-6. PMID:15651203
5. ↑ Aronson NN Jr. Aspartylglycosaminuria: biochemistry and molecular biology. Biochim Biophys Acta. 1999 Oct 8;1455(2-3):139-54. PMID:10571008
6. ↑ Yun MK, Nourse A, White SW, Rock CO, Heath RJ. Crystal structure and allosteric regulation of the cytoplasmic Escherichia coli L-asparaginase I. J Mol Biol. 2007 Jun 8;369(3):794-811. Epub 2007 Mar 30. PMID:17451745 doi:http://dx.doi.org/10.1016/j.jmb.2007.03.061