8r6t

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'''Unreleased structure'''
 
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The entry 8r6t is ON HOLD
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==NMR solution structure of thyropin IrThy-Cd from the hard tick Ixodes ricinus==
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<StructureSection load='8r6t' size='340' side='right'caption='[[8r6t]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8r6t]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Ixodes_ricinus Ixodes ricinus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8R6T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8R6T FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 30 models</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8r6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8r6t OCA], [https://pdbe.org/8r6t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8r6t RCSB], [https://www.ebi.ac.uk/pdbsum/8r6t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8r6t ProSAT]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The structure and biochemical properties of protease inhibitors from the thyropin family are poorly understood in parasites and pathogens. Here, we introduce a novel family member, Ir-thyropin (IrThy), which is secreted in the saliva of Ixodes ricinus ticks, vectors of Lyme borreliosis and tick-borne encephalitis. The IrThy molecule consists of two consecutive thyroglobulin type-1 (Tg1) domains with an unusual disulfide pattern. Recombinant IrThy was found to inhibit human host-derived cathepsin proteases with a high specificity for cathepsins V, K, and L among a wide range of screened cathepsins exhibiting diverse endo- and exopeptidase activities. Both Tg1 domains displayed inhibitory activities, but with distinct specificity profiles. We determined the spatial structure of one of the Tg1 domains by solution NMR spectroscopy and described its reactive center to elucidate the unique inhibitory specificity. Furthermore, we found that the inhibitory potency of IrThy was modulated in a complex manner by various glycosaminoglycans from host tissues. IrThy was additionally regulated by pH and proteolytic degradation. This study provides a comprehensive structure-function characterization of IrThy-the first investigated thyropin of parasite origin-and suggests its potential role in host-parasite interactions at the tick bite site.
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Authors:
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An Unusual Two-Domain Thyropin from Tick Saliva: NMR Solution Structure and Highly Selective Inhibition of Cysteine Cathepsins Modulated by Glycosaminoglycans.,Matouskova Z, Orsaghova K, Srb P, Pytelkova J, Kukacka Z, Busa M, Hajdusek O, Sima R, Fabry M, Novak P, Horn M, Kopacek P, Mares M Int J Mol Sci. 2024 Feb 13;25(4):2240. doi: 10.3390/ijms25042240. PMID:38396918<ref>PMID:38396918</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 8r6t" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Ixodes ricinus]]
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[[Category: Large Structures]]
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[[Category: Mares M]]
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[[Category: Matouskova Z]]
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[[Category: Orsaghova K]]
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[[Category: Srb P]]
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[[Category: Veverka V]]

Current revision

NMR solution structure of thyropin IrThy-Cd from the hard tick Ixodes ricinus

PDB ID 8r6t

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