View source for 5k45


==Wolinella succinogenes L-asparaginase P121 + L-Glutamic acid==
<StructureSection load='5k45' size='340' side='right'caption='[[5k45]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5k45]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Wolinella_succinogenes_DSM_1740 Wolinella succinogenes DSM 1740]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K45 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K45 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]] 1.63&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</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=5k45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k45 OCA], [https://pdbe.org/5k45 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k45 RCSB], [https://www.ebi.ac.uk/pdbsum/5k45 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k45 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ASPG_WOLSU ASPG_WOLSU] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Many side effects of current FDA-approved L-asparaginases have been related to their secondary L-glutaminase activity. The Wolinella succinogenes L-asparaginase (WoA) has been reported to be L-glutaminase free, suggesting it would have fewer side effects. Unexpectedly, the WoA variant with a proline at position 121 (WoA-P121) was found to have L-glutaminase activity in contrast to Uniprot entry P50286 (WoA-S121) that has a serine residue at this position. Towards understanding how this residue impacts the L-glutaminase property, kinetic analysis was coupled with crystal structure determination of these WoA variants. WoA-S121 was confirmed to have much lower L-glutaminase activity than WoA-P121, yet both showed comparable L-asparaginase activity. Structures of the WoA variants in complex with L-aspartic acid versus L-glutamic acid provide insights into their differential substrate selectivity. Structural analysis suggests a mechanism by which residue 121 impacts the conformation of the conserved tyrosine 27, a component of the catalytically-important flexible N-terminal loop. Surprisingly, we could fully model this loop in either its open or closed conformations, revealing the roles of specific residues of an evolutionary conserved motif among this L-asparaginase family. Together, this work showcases critical residues that influence the ability of the flexible N-terminal loop for adopting its active conformation, thereby effecting substrate specificity.

The differential ability of asparagine and glutamine in promoting the closed/active enzyme conformation rationalizes the Wolinella succinogenes L-asparaginase substrate specificity.,Nguyen HA, Durden DL, Lavie A Sci Rep. 2017 Jan 31;7:41643. doi: 10.1038/srep41643. PMID:28139703<ref>PMID:28139703</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5k45" style="background-color:#fffaf0;"></div>

==See Also==
*[[Asparaginase 3D structures|Asparaginase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Wolinella succinogenes DSM 1740]]
[[Category: Lave A]]
[[Category: Nguyen HA]]