6klm: Difference between revisions

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-'''Unreleased structure'''
-The entry 6klm is ON HOLD
+==NMR solution structure of Roseltide rT7==
+<StructureSection load='6klm' size='340' side='right'caption='[[6klm]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6klm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Hibiscus_sabdariffa Hibiscus sabdariffa]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KLM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KLM FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 17 models</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=6klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6klm OCA], [https://pdbe.org/6klm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6klm RCSB], [https://www.ebi.ac.uk/pdbsum/6klm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6klm ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Disulfide-rich plant peptides with molecular weights of 2 to 6 kDa represent an expanding class of peptidyl-type natural products with diverse functions. They are structurally compact, hyperstable, and underexplored as cell-penetrating agents that inhibit intracellular functions. Here, we report the discovery of an anionic, 34-residue-peptide, the disulfide-rich roseltide rT7 from Hibiscus sabdariffa (of the Malvaceae family), that penetrates cells and inhibits their proteasomal activities. Combined proteomics and NMR spectroscopy revealed that roseltide rT7 is a cystine-knotted, 6C-hevein-like cysteine-rich peptide. A pair-wise comparison indicated that roseltide rT7 is &gt; 100-fold more stable against protease degradation than its S-alkylated analog. Confocal microscopy studies and cell-based assays disclosed that after roseltide rT7 penetrates cells, it causes accumulation of ubiquitinated proteins, inhibits human 20S proteasomes, reduces tumor necrosis factor-induced IkappaBC; degradation, and decreases expression levels of intercellular adhesion molecule-1. Structure-activity studies revealed that roseltide rT7 uses a canonical substrate-binding mechanism for proteasomal inhibition enabled by an IIML motif embedded in its proline-rich and exceptionally long intercysteine loop 4. Taken together, our results provide mechanistic insights into a novel disulfide-rich, anionic, and cell-penetrating peptide, representing a potential lead for further development as a proteasomal inhibitor in anti-cancer or anti-inflammatory therapies.
-Authors:
+Roseltide rT7 is a disulfide-rich, anionic, and cell-penetrating peptide that inhibits proteasomal degradation.,Kam A, Loo S, Fan JS, Sze SK, Yang D, Tam JP J Biol Chem. 2019 Nov 14. pii: RA119.010796. doi: 10.1074/jbc.RA119.010796. PMID:31727740<ref>PMID:31727740</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6klm" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Hibiscus sabdariffa]]
+[[Category: Large Structures]]
+[[Category: Fan JS]]
+[[Category: Kam A]]
+[[Category: Loo S]]
+[[Category: Tam PJ]]
+[[Category: Yang D]]