Asparaginase: Difference between revisions
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<StructureSection load='' size='300' side='right' scene='52/525144/Class_ii_3eca/2' caption='First Asparaginase structure (Class_II - [3eca]) dimer, [[3eca]]'> | |||
__TOC__ | __TOC__ | ||
== Function == | == 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. | '''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. | ||
*'''Glycosylasparaginase''' hydrolyzes the bond between asparagine and the sugar moiety in N-linked glycoproteins<ref>PMID:8638940</ref>. | |||
*'''Isoaspartyl peptidase/L-asparaginase''' enables aparaginase and beta-aspartyl-peptidase activity. Invovved in asparagine catabolic process via L-Asp <ref>PMID:15159592</ref>. | |||
== Relevance == | == Relevance == | ||
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== Structural studies == | == Structural studies == | ||
The first L-asparaginase structure was published and deposited in the PDB in 1993 for the EcAII enzyme <ref>PMID:8434007</ref> and may serve as an example of a | The first L-asparaginase structure was published and deposited in the PDB in 1993 for the EcAII enzyme <ref>PMID:8434007</ref> and may serve as an example of a <scene name='52/525144/Class_ii_5os5/2'>Class 1 type II enzyme EcAII</scene>. Structure of <scene name='52/525144/Class_i_8oww/2'>Class 1 type I enzymes is exemplified by EcAI</scene><ref>PMID:17451745</ref>, whereas <scene name='52/525144/Ecaiii_2zal/4'>Class 2 type III enzymes may be represented by EcAIII</scene><ref>PMID:15159592</ref><ref>PMID:18334484</ref>. Class 2 L-asparaginases belong to the family of Ntn-hydrolases, which are expressed as inactive precursors that must undergo autoproteolytic cleavage into α and β subunits to achieve maturation<ref>PMID:35626629</ref>. While the existence of an alien type of ASNase in the symbiotic nitrogen-fixing bacterium ''Rhizobium etli'' had been recognized long ago<ref>PMID:11996000</ref>, the structure of the <scene name='52/525144/Class_ii_5os5/2'>iducible and thermolabile prototype Class 3 ReAV</scene> was solved and deposited in the PDB only recently<ref>PMID:34795296</ref>, followed by structures of the constitutive and <scene name='52/525144/8sow/1'>thermostable isoform ReAIV</scene><ref>PMID:37494066</ref>. More than 200 structures of ASNases have been deposited in the Protein Data Bank (PDB) by April 2024<ref>PMID:34060231</ref><ref name="Wlodawer">Wlodawer, A., Dauter, Z., Lubkowski, J., Loch, J.I., Brzezinski, D., Gilski, M., Jaskolski, M. (2024) Toward a dependable dataset of structures for L-asparaginase research(submitted).</ref>. | ||
== Evaluation of the ASNase structures in the PDB == | == Evaluation of the ASNase structures in the PDB == | ||
Evaluation of 189 structures of ASNases that were present in the PDB as of November 2023 was described in Wlodawer et al. (2024). Most structures did not raise any significant concerns. However, 30 models had various kinds of stereochemical problems and/or doubtful agreement with the experimental electron density maps. Consequently, they were re-refined in order to remove the shortcomings. The revised models (listed here) may be downloaded from this site in both the legacy PDB and mmCIF formats. | Evaluation of 189 structures of ASNases that were present in the PDB as of November 2023 was described in Wlodawer et al. (2024)<ref name="Wlodawer" />. Most structures did not raise any significant concerns. However, 30 models had various kinds of stereochemical problems and/or doubtful agreement with the experimental electron density maps. Consequently, they were re-refined in order to remove the shortcomings. The revised models (listed here) may be downloaded from this site in both the legacy PDB and mmCIF formats. | ||
==3D structures of asparaginase== | ==3D structures of asparaginase== | ||