5k3o: Difference between revisions

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~~'''Unreleased structure'''~~

The entry ~~5k3o is ON HOLD~~

==Wolinella succinogenes L-asparaginase P121 and L-Aspartic acid==

== Structural highlights ==

<table><tr><td colspan='2'>[[5k3o]] 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=5K3O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K3O 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]] 1.696Å</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=5k3o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k3o OCA], [https://pdbe.org/5k3o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k3o RCSB], [https://www.ebi.ac.uk/pdbsum/5k3o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k3o ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/ASPG_WOLSU ASPG_WOLSU]

== 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.

~~Authors~~:

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>

~~Description~~:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

==See Also==

*[[Asparaginase 3D structures|Asparaginase 3D structures]]

== References ==

__TOC__

</StructureSection>

[[Category: Large Structures]]

[[Category: Wolinella succinogenes DSM 1740]]

[[Category: Lave A]]

[[Category: Nguyen HA]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5k3o is ON HOLD
+==Wolinella succinogenes L-asparaginase P121 and L-Aspartic acid==
+<StructureSection load='5k3o' size='340' side='right'caption='[[5k3o]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5k3o]] 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=5K3O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K3O 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]] 1.696&#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=5k3o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k3o OCA], [https://pdbe.org/5k3o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k3o RCSB], [https://www.ebi.ac.uk/pdbsum/5k3o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k3o 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.
-Authors:
+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>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5k3o" 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]]