View source for 8ums


==Site-specific Aspartic Acid Dehydration and Isomerization in Streptococcal Protein GB1: L-isoAsp40 Variant==
<StructureSection load='8ums' size='340' side='right'caption='[[8ums]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ums]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus Streptococcus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8UMS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UMS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 10 models</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IAS:BETA-L-ASPARTIC+ACID'>IAS</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=8ums FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ums OCA], [https://pdbe.org/8ums PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ums RCSB], [https://www.ebi.ac.uk/pdbsum/8ums PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ums ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SPG2_STRSG SPG2_STRSG] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Chemical modifications of long-lived proteins, such as isomerization and epimerization, have been evoked as prime triggers for protein-damage related diseases. Deamidation of Asn residues, which results in formation of a mixture of l- and d-Asp and isoAsp via an intermediate aspartyl succinimide, can result in the disruption of cellular proteostasis and toxic protein depositions. In contrast to extensive data on the biological prevalence and functional implications of aspartyl succinimide formation, much less is known about the impact of the resulting altered backbone composition on properties of individual proteins at a molecular level. Here, we report the total chemical synthesis, biophysical characterization, and NMR structural analysis of a series of variants of the B1 domain of protein G from Streptococcal bacteria (GB1) in which all possible Asp isomers as well as an aspartyl succinimide were individually incorporated at a defined position in a solvent-exposed loop. Subtle local structural effects were observed; however, these were accompanied by notable differences in thermodynamic folded stability. Surprisingly, the noncanonical backbone connectivity of d-isoAsp led to a variant that exhibited enhanced stability relative to the natural protein.

Probing effects of site-specific aspartic acid isomerization on structure and stability of GB1 through chemical protein synthesis.,Heath SL, Guseman AJ, Gronenborn AM, Horne WS Protein Sci. 2024 Mar;33(3):e4883. doi: 10.1002/pro.4883. PMID:38143426<ref>PMID:38143426</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ums" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptococcus]]
[[Category: Gronenborn AM]]
[[Category: Guseman AJ]]
[[Category: Heath SL]]
[[Category: Horne WS]]