Asparaginase: Difference between revisions
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<StructureSection load='' size='300' side='right' scene='52/525144/ | <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 Class 1 type II enzyme | 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 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== | ||