We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

Asparaginase

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 08:36, 29 April 2024

E. coli asparaginase I tetramer complex with aspartic acid, asparagine, ethylene glycol and Cl- ions (green), 2p2n

Drag the structure with the mouse to rotate

1 Function
2 Relevance
3 Division of ASNases into three classes
4 Structural highlights
5 3D structures of 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.

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]^[1]^[2]^[3]^[4]. 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].

Division of ASNases into three classes

So far, three completely different structural classes of ASNases have been identified^[7], originally named according to the source organism of their isolation^[8], 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).

Structural highlights

.^[9] 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

↑ 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
↑ Chan WK, Horvath TD, Tan L, Link T, Harutyunyan KG, Pontikos MA, Anishkin A, Du D, Martin LA, Yin E, Rempe SB, Sukharev S, Konopleva M, Weinstein JN, Lorenzi PL. Glutaminase Activity of L-Asparaginase Contributes to Durable Preclinical Activity against Acute Lymphoblastic Leukemia. Mol Cancer Ther. 2019 Sep;18(9):1587-1592. PMID:31209181 doi:10.1158/1535-7163.MCT-18-1329
↑ 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
↑ 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

Proteopedia Page Contributors and Editors (what is this?)

Joel L. Sussman, Michal Harel, Alexander Berchansky, Jaime Prilusky

Retrieved from "http://52.214.119.220/wiki/index.php/Asparaginase"

Category: Topic Page

@@ Line 11: / Line 11: @@
 == Division of ASNases into three classes ==
-So far, three completely different structural classes of ASNases have been identified<ref>PMID:34258001</ref>, originally named according to the source organism of their isolation [8], 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).<ref>PMID:10571008</ref>.
+So far, three completely different structural classes of ASNases have been identified<ref>PMID:34258001</ref>, originally named according to the source organism of their isolation<ref>PMID:17143335</ref>, 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).
 == Structural highlights ==

Asparaginase

From Proteopedia

Revision as of 08:36, 29 April 2024

Contents

Function

Relevance

Division of ASNases into three classes

Structural highlights

3D structures of asparaginase

References

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox