We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.
8bww
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | == | + | ==Targeting Toll-like receptor-driven systemic inflammation by engineering an innate structural fold into drugs== |
<StructureSection load='8bww' size='340' side='right'caption='[[8bww]]' scene=''> | <StructureSection load='8bww' size='340' side='right'caption='[[8bww]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8bww]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BWW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BWW FirstGlance]. <br> | <table><tr><td colspan='2'>[[8bww]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BWW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BWW 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> | + | </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=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</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=8bww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bww OCA], [https://pdbe.org/8bww PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bww RCSB], [https://www.ebi.ac.uk/pdbsum/8bww PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bww ProSAT]</span></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=8bww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bww OCA], [https://pdbe.org/8bww PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bww RCSB], [https://www.ebi.ac.uk/pdbsum/8bww PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bww ProSAT]</span></td></tr> | ||
| Line 12: | Line 12: | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref> | [https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | There is a clinical need for conceptually new treatments that target the excessive activation of inflammatory pathways during systemic infection. Thrombin-derived C-terminal peptides (TCPs) are endogenous anti-infective immunomodulators interfering with CD14-mediated TLR-dependent immune responses. Here we describe the development of a peptide-based compound for systemic use, sHVF18, expressing the evolutionarily conserved innate structural fold of natural TCPs. Using a combination of structure- and in silico-based design, nuclear magnetic resonance spectroscopy, biophysics, mass spectrometry, cellular, and in vivo studies, we here elucidate the structure, CD14 interactions, protease stability, transcriptome profiling, and therapeutic efficacy of sHVF18. The designed peptide displays a conformationally stabilized, protease resistant active innate fold and targets the LPS-binding groove of CD14. In vivo, it shows therapeutic efficacy in experimental models of endotoxin shock in mice and pigs and increases survival in mouse models of systemic polymicrobial infection. The results provide a drug class based on Nature s own anti-infective principles. | ||
| + | |||
| + | Targeting Toll-like receptor-driven systemic inflammation by engineering an innate structural fold into drugs.,Petruk G, Puthia M, Samsudin F, Petrlova J, Olm F, Mittendorfer M, Hyllen S, Edstrom D, Stromdahl AC, Diehl C, Ekstrom S, Walse B, Kjellstrom S, Bond PJ, Lindstedt S, Schmidtchen A Nat Commun. 2023 Sep 29;14(1):6097. doi: 10.1038/s41467-023-41702-y. PMID:37773180<ref>PMID:37773180</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8bww" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Targeting Toll-like receptor-driven systemic inflammation by engineering an innate structural fold into drugs
| |||||||||||
