5i48: Difference between revisions
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<StructureSection load='5i48' size='340' side='right'caption='[[5i48]], [[Resolution|resolution]] 1.50Å' scene=''> | <StructureSection load='5i48' size='340' side='right'caption='[[5i48]], [[Resolution|resolution]] 1.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5i48]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5i48]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Dickeya_chrysanthemi Dickeya chrysanthemi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I48 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASP:ASPARTIC+ACID'>ASP</scene></td></tr> | |||
<tr id=' | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5i48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i48 OCA], [https://pdbe.org/5i48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i48 RCSB], [https://www.ebi.ac.uk/pdbsum/5i48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i48 ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/ASPG_DICCH ASPG_DICCH] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Current FDA-approved l-asparaginases also possess significant l-glutaminase activity, which correlates with many of the toxic side effects of these drugs. Therefore, l-asparaginases with reduced l-glutaminase activity are predicted to be safer. We exploited our recently described structures of the Erwinia chrysanthemi l-asparaginase (ErA) to inform the design of mutants with diminished ability to hydrolyze l-glutamine. Structural analysis of these variants provides insight into the molecular basis for the increased l-asparagine specificity. A primary role is attributed to the E63Q mutation that acts to hinder the correct positioning of l-glutamine but not l-asparagine. The substitution of Ser-254 with either an asparagine or a glutamine increases the l-asparagine specificity but only when combined with the E63Q mutation. The A31I mutation reduces the substrate Km value; this is a key property to allow the required therapeutic l-asparagine depletion. Significantly, an ultra-low l-glutaminase ErA variant maintained its cell killing ability. By diminishing the l-glutaminase activity of these highly active l-asparaginases, our engineered ErA variants hold promise as l-asparaginases with fewer side effects. | |||
Design and Characterization of Erwinia Chrysanthemi l-Asparaginase Variants with Diminished l-Glutaminase Activity.,Nguyen HA, Su Y, Lavie A J Biol Chem. 2016 Aug 19;291(34):17664-76. doi: 10.1074/jbc.M116.728485. Epub , 2016 Jun 27. PMID:27354283<ref>PMID:27354283</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5i48" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Asparaginase 3D structures|Asparaginase 3D structures]] | *[[Asparaginase 3D structures|Asparaginase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Dickeya chrysanthemi]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Lavie | [[Category: Lavie A]] | ||
[[Category: Nguyen | [[Category: Nguyen HA]] | ||
Latest revision as of 08:22, 23 August 2023
Erwinia chrysanthemi L-asparaginase A31I + E63Q mutation + Aspartic acid
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