7vhc: Difference between revisions
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==Crystal structure of the STX2a complexed with AR4A peptide== | |||
<StructureSection load='7vhc' size='340' side='right'caption='[[7vhc]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7vhc]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VHC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VHC 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]] 1.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PS:3-PYRIDINIUM-1-YLPROPANE-1-SULFONATE'>1PS</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=7vhc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vhc OCA], [https://pdbe.org/7vhc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vhc RCSB], [https://www.ebi.ac.uk/pdbsum/7vhc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vhc ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q7DI68_ECO57 Q7DI68_ECO57] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Shiga toxin (Stx), a major virulence factor of enterohemorrhagic Escherichia coli (EHEC), can cause fatal systemic complications. Recently, we identified a potent inhibitory peptide that binds to the catalytic A-subunit of Stx. Here, using biochemical structural analysis and X-ray crystallography, we determined a minimal essential peptide motif that occupies the catalytic cavity and is required for binding to the A-subunit of Stx2a, a highly virulent Stx subtype. Molecular dynamics simulations also identified the same motif and allowed determination of a unique pharmacophore for A-subunit binding. Notably, a series of synthetic peptides containing the motif efficiently inhibit Stx2a. In addition, pharmacophore screening and subsequent docking simulations ultimately identified nine Stx2a-interacting molecules out of a chemical compound database consisting of over 7,400,000 molecules. Critically, one of these molecules markedly inhibits Stx2a both in vitro and in vivo, clearly demonstrating the significance of the pharmacophore for identifying therapeutic agents against EHEC infection. | |||
A unique peptide-based pharmacophore identifies an inhibitory compound against the A-subunit of Shiga toxin.,Watanabe-Takahashi M, Senda M, Yoshino R, Hibino M, Hama S, Terada T, Shimizu K, Senda T, Nishikawa K Sci Rep. 2022 Jul 6;12(1):11443. doi: 10.1038/s41598-022-15316-1. PMID:35794188<ref>PMID:35794188</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7vhc" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Shiga toxin 3D structures|Shiga toxin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Nishikawa K]] | |||
[[Category: Senda M]] | |||
[[Category: Senda T]] | |||
[[Category: Takahashi M]] | |||
Latest revision as of 09:51, 21 November 2024
Crystal structure of the STX2a complexed with AR4A peptideCrystal structure of the STX2a complexed with AR4A peptide
Structural highlights
FunctionPublication Abstract from PubMedShiga toxin (Stx), a major virulence factor of enterohemorrhagic Escherichia coli (EHEC), can cause fatal systemic complications. Recently, we identified a potent inhibitory peptide that binds to the catalytic A-subunit of Stx. Here, using biochemical structural analysis and X-ray crystallography, we determined a minimal essential peptide motif that occupies the catalytic cavity and is required for binding to the A-subunit of Stx2a, a highly virulent Stx subtype. Molecular dynamics simulations also identified the same motif and allowed determination of a unique pharmacophore for A-subunit binding. Notably, a series of synthetic peptides containing the motif efficiently inhibit Stx2a. In addition, pharmacophore screening and subsequent docking simulations ultimately identified nine Stx2a-interacting molecules out of a chemical compound database consisting of over 7,400,000 molecules. Critically, one of these molecules markedly inhibits Stx2a both in vitro and in vivo, clearly demonstrating the significance of the pharmacophore for identifying therapeutic agents against EHEC infection. A unique peptide-based pharmacophore identifies an inhibitory compound against the A-subunit of Shiga toxin.,Watanabe-Takahashi M, Senda M, Yoshino R, Hibino M, Hama S, Terada T, Shimizu K, Senda T, Nishikawa K Sci Rep. 2022 Jul 6;12(1):11443. doi: 10.1038/s41598-022-15316-1. PMID:35794188[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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