Asparaginase: Difference between revisions

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

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 == 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 <scene name='52/525144/3eca_cartoon/8'>EcAII</scene>. Structure of Class 1 type I enzymes is exemplified by <scene name='52/525144/Ecai_2p2n/3'>EcAI</scene><ref>PMID:17451745</ref>, whereas Class 2 type III enzymes may be represented by <scene name='52/525144/Ecaiii_2zal/3'>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 inducible and thermolabile prototype <scene name='52/525144/Reav_7os5/1'>Class 3 ReAV</scene> was solved and deposited in the PDB only recently<ref>PMID:34795296</ref>, followed by structures of the constitutive and thermostable isoform ReAIV<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>Wlodawer, A., Dauter, Z., Lubkowski, J.,  Loch, J.I., Brzezinski, D., Gilski, M., Jaskolsk, M. (2024) Toward a dependable dataset of structures for L-asparaginase research(submitted).</ref>.
+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 <scene name='52/525144/3eca_cartoon/8'>EcAII</scene>. Structure of Class 1 type I enzymes is exemplified by <scene name='52/525144/Ecai_2p2n/3'>EcAI</scene><ref>PMID:17451745</ref>, whereas Class 2 type III enzymes may be represented by <scene name='52/525144/Ecaiii_2zal/3'>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 inducible and thermolabile prototype <scene name='52/525144/Reav_7os5/1'>Class 3 ReAV</scene> was solved and deposited in the PDB only recently<ref>PMID:34795296</ref>, followed by structures of the constitutive and thermostable isoform ReAIV<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., Jaskolsk, 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). 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.