View source for 8hr3


==[D-Cys5,Asp7,Val8,D-Lys16]-STp(5-17)==
<StructureSection load='8hr3' size='340' side='right'caption='[[8hr3]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8hr3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8HR3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HR3 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DCY:D-CYSTEINE'>DCY</scene>, <scene name='pdbligand=DLY:D-LYSINE'>DLY</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=8hr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hr3 OCA], [https://pdbe.org/8hr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hr3 RCSB], [https://www.ebi.ac.uk/pdbsum/8hr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hr3 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Heat-stable enterotoxin (ST(a)) produced by Enterotoxigenic E. coli is responsible for causing acute diarrhea in infants in developing countries. However, the chemical synthesis of ST(a) peptides with the native conformation and the correct intra-molecular disulfide bonds is a major hurdle for vaccine development. To address this issue, we herein report on the design and preparation of ST(a) analogs and a convenient chemical method for obtaining ST(a) molecules with the correct conformation. To develop an ST(a) vaccine, we focused on a structure in a type II beta-turn in the ST(a) molecule and introduced a D-Lys residue as a conjugation site for carrier proteins. In addition, the -Glu-Leu- sequence in the ST(a) molecule was replaced with a -Asp-Val- sequence to decrease the toxic activity of the peptide to make it more amenable for use in vaccinations. To solve several issues associated with the synthesis of ST(a), such as the formation of non-native disulfide isomers, the native disulfide pairings were regioselectively formed in a stepwise manner. A native form or topological isomer of the designed ST(a) peptide, which possesses a right-handed or a left-handed spiral structure, respectively, were synthesized in high synthetic yields. The conformation of the synthetic ST(a) peptide was also confirmed by CD and NMR spectroscopy. To further utilize the designed ST(a) peptide, it was labeled with fluorescein for fluorescent detection, since recent studies have also focused on the use of ST(a) for detecting cancer cells, such as Caco-2 and T84. The labeled ST(a) peptide was able to specifically and efficiently detect 293T cells expressing the recombinant ST(a) receptor (GC-C) protein and Caco-2 cells. The findings reported here provide an outline of the molecular basis for using ST(a) for vaccine development and in the detection of cancer cells.

The Molecular Basis of Heat-Stable Enterotoxin for Vaccine Development and Cancer Cell Detection.,Goto M, Yoshino S, Hiroshima K, Kawakami T, Murota K, Shimamoto S, Hidaka Y Molecules. 2023 Jan 23;28(3):1128. doi: 10.3390/molecules28031128. PMID:36770798<ref>PMID:36770798</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8hr3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Goto M]]
[[Category: Hidaka Y]]
[[Category: Shimamoto S]]
[[Category: Yoshino S]]