View source for 5i48


==Erwinia chrysanthemi L-asparaginase A31I + E63Q mutation + Aspartic acid==
<StructureSection load='5i48' size='340' side='right'caption='[[5i48]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</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='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>
</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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5i48" style="background-color:#fffaf0;"></div>

==See Also==
*[[Asparaginase 3D structures|Asparaginase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dickeya chrysanthemi]]
[[Category: Large Structures]]
[[Category: Lavie A]]
[[Category: Nguyen HA]]