6kmc: Difference between revisions
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==Crystal structure of a Streptococcal protein G B1 mutant== | |||
<StructureSection load='6kmc' size='340' side='right'caption='[[6kmc]], [[Resolution|resolution]] 1.84Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6kmc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_sp._'group_G' Streptococcus sp. 'group G']. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KMC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KMC 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]] 1.84Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</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=6kmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kmc OCA], [https://pdbe.org/6kmc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kmc RCSB], [https://www.ebi.ac.uk/pdbsum/6kmc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kmc ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SPG2_STRSG SPG2_STRSG] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Protein-protein interactions that can be controlled by environmental triggers have immense potential in various biological and industrial applications. In the current study, we aimed to engineer a pH-dependent protein-protein interaction that employs intramolecular electrostatic repulsion through a structure-guided histidine substitution approach. We implemented this strategy on Streptococcal protein G, an affinity ligand for immunoglobulin G, and showed that even a single point mutation effectively improved the pH sensitivity of the binding interactions without adversely affecting its structural stability or its innate binding function. Depending on the pH of the environment, the protein-protein interaction was disrupted by the electrostatic repulsion between the substituted histidine and its neighboring positively charged residues. Structurally, the substituted histidine residue was located adjacent to a lysine residue that could form hydrogen bonds with immunoglobulin G. Thermodynamically, the introduced electrostatic repulsion was reflected in the significant loss of the exothermic heat of the binding under acidic conditions, whereas accompanying enthalpy-entropy compensation partly suppressed the improvement of the pH sensitivity. Thus, the engineered pH-sensitive protein G could enable antibody purification under mildly acidic conditions. This intramolecular design can be combined with conventional protein-protein interface design. Moreover, the method proposed here provides us with additional design criteria for optimization of pH-dependent molecular interactions. | |||
Histidine-Mediated Intramolecular Electrostatic Repulsion for Controlling pH-Dependent Protein-Protein Interaction.,Watanabe H, Yoshida C, Ooishi A, Nakai Y, Ueda M, Isobe Y, Honda S ACS Chem Biol. 2019 Oct 22. doi: 10.1021/acschembio.9b00652. PMID:31596562<ref>PMID:31596562</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6kmc" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Protein G|Protein G]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Streptococcus sp. 'group G']] | |||
[[Category: Honda S]] | |||
[[Category: Watanabe H]] | |||