Toward a dependable data set of structures for L-asparaginase
Alexander Wlodawer, Zbigniew Dauter, Jacek Lubkowski, Joanna I. Loch, Dariusz Brzezinski, Miroslaw Gilski, Mariusz Jaskolski [1]
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.
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)[2][3][4][5]. 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[6][7].
Division of ASNases into three classes
So far, three completely different structural classes of ASNases have been identified[8], originally named according to the source organism of their isolation[9], namely Class 1 (bacterial-type), Class 2 (plant-type), and Class 3 (Rhizobium etli-type). This newer classification is intersected with an older convention, which divided the known enzymes with L-asparaginase activity into five types, since in both, Class 1 and Class 3, two types are distinguished according to their compartmentalization and expression profile. The prototypes of types I and II (in Class 1), and III (in Class 2), are the E. coli enzymes EcAI (cytosolic), EcAII (periplasmic), and EcAIII (also cytosolic), respectively. The prototypes of types IV and V (Class 3) are the R. etli enzymes ReAIV (constitutive) and ReAV (inducible).
Dependable Structures
Download Deposited Dependable Aligned
References
- ↑ Wlodawer A, Dauter Z, Lubkowski J, Loch JI, Brzezinski D, Gilski M, Jaskolski M. Towards a dependable data set of structures for L-asparaginase research. Acta Crystallogr D Struct Biol. 2024 Jul 1;80(Pt 7):506-527. PMID:38935343 doi:10.1107/S2059798324005461
- ↑ Egler RA, Ahuja SP, Matloub Y. L-asparaginase in the treatment of patients with acute lymphoblastic leukemia. J Pharmacol Pharmacother. 2016 Apr-Jun;7(2):62-71. PMID:27440950 doi:10.4103/0976-500X.184769
- ↑ Beckett A, Gervais D. What makes a good new therapeutic L-asparaginase? World J Microbiol Biotechnol. 2019 Sep 24;35(10):152. PMID:31552479 doi:10.1007/s11274-019-2731-9
- ↑ Ghasemian A, Al-Marzoqi AH, Al-Abodi HR, Alghanimi YK, Kadhum SA, Shokouhi Mostafavi SK, Fattahi A. Bacterial l-asparaginases for cancer therapy: Current knowledge and future perspectives. J Cell Physiol. 2019 Nov;234(11):19271-19279. PMID:30993718 doi:10.1002/jcp.28563
- ↑ Chand S, Mahajan RV, Prasad JP, Sahoo DK, Mihooliya KN, Dhar MS, Sharma G. A comprehensive review on microbial l-asparaginase: Bioprocessing, characterization, and industrial applications. Biotechnol Appl Biochem. 2020 Jul;67(4):619-647. PMID:31954377 doi:10.1002/bab.1888
- ↑ Hendriksen HV, Kornbrust BA, Østergaard PR, Stringer MA. Evaluating the potential for enzymatic acrylamide mitigation in a range of food products using an asparaginase from Aspergillus oryzae. J Agric Food Chem. 2009 May 27;57(10):4168-76. PMID:19388639 doi:10.1021/jf900174q
- ↑ Chand S, Mahajan RV, Prasad JP, Sahoo DK, Mihooliya KN, Dhar MS, Sharma G. A comprehensive review on microbial l-asparaginase: Bioprocessing, characterization, and industrial applications. Biotechnol Appl Biochem. 2020 Jul;67(4):619-647. PMID:31954377 doi:10.1002/bab.1888
- ↑ Loch JI, Jaskolski M. Structural and biophysical aspects of l-asparaginases: a growing family with amazing diversity. IUCrJ. 2021 Jun 30;8(Pt 4):514-531. PMID:34258001 doi:10.1107/S2052252521006011
- ↑ Michalska K, Jaskolski M. Structural aspects of L-asparaginases, their friends and relations. Acta Biochim Pol. 2006;53(4):627-40. Epub 2006 Dec 1 PMID:17143335
