5gsf: Difference between revisions
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==Structure of roseltide rT1== | |||
<StructureSection load='5gsf' size='340' side='right' caption='[[5gsf]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5gsf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Hibiscus_sabdariffa Hibiscus sabdariffa]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GSF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GSF FirstGlance]. <br> | |||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5gsf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gsf OCA], [http://pdbe.org/5gsf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gsf RCSB], [http://www.ebi.ac.uk/pdbsum/5gsf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gsf ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Plant knottins are of therapeutic interest due to their high metabolic stability and inhibitory activity against proteinases involved in human diseases. The only knottin-type proteinase inhibitor against porcine pancreatic elastase was first identified from the squash family in 1989. Here, we report the identification and characterization of a knottin-type human neutrophil elastase inhibitor from Hibiscus sabdariffa of the Malvaceae family. Combining proteomic and transcriptomic methods, we identified a panel of novel cysteine-rich peptides, roseltides (rT1-rT8), which range from 27 to 39 residues with six conserved cysteine residues. The 27-residue roseltide rT1 contains a cysteine spacing and amino acid sequence that is different from the squash knottin-type elastase inhibitor. NMR analysis demonstrated that roseltide rT1 adopts a cystine-knot fold. Transcriptome analyses suggested that roseltides are bioprocessed by asparagine endopeptidases from a three-domain precursor. The cystine-knot structure of roseltide rT1 confers its high resistance against degradation by endopeptidases, 0.2 N HCl, and human serum. Roseltide rT1 was shown to inhibit human neutrophil elastase using enzymatic and pull-down assays. Additionally, roseltide rT1 ameliorates neutrophil elastase-stimulated cAMP accumulation in vitro. Taken together, our findings demonstrate that roseltide rT1 is a novel knottin-type neutrophil elastase inhibitor with therapeutic potential for neutrophil elastase associated diseases. | |||
Identification and Characterization of Roseltide, a Knottin-type Neutrophil Elastase Inhibitor Derived from Hibiscus sabdariffa.,Loo S, Kam A, Xiao T, Nguyen GK, Liu CF, Tam JP Sci Rep. 2016 Dec 19;6:39401. doi: 10.1038/srep39401. PMID:27991569<ref>PMID:27991569</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5gsf" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Hibiscus sabdariffa]] | |||
[[Category: Tam, J P]] | |||
[[Category: Xiao, T]] | [[Category: Xiao, T]] | ||
[[Category: | [[Category: Cysteine rich peptide]] | ||
[[Category: Hydrolase inhibitor]] | |||
[[Category: Neutrophil elastase inhibitor]] | |||
[[Category: Roseltide]] | |||
Revision as of 02:34, 26 January 2017
Structure of roseltide rT1Structure of roseltide rT1
Structural highlights
Publication Abstract from PubMedPlant knottins are of therapeutic interest due to their high metabolic stability and inhibitory activity against proteinases involved in human diseases. The only knottin-type proteinase inhibitor against porcine pancreatic elastase was first identified from the squash family in 1989. Here, we report the identification and characterization of a knottin-type human neutrophil elastase inhibitor from Hibiscus sabdariffa of the Malvaceae family. Combining proteomic and transcriptomic methods, we identified a panel of novel cysteine-rich peptides, roseltides (rT1-rT8), which range from 27 to 39 residues with six conserved cysteine residues. The 27-residue roseltide rT1 contains a cysteine spacing and amino acid sequence that is different from the squash knottin-type elastase inhibitor. NMR analysis demonstrated that roseltide rT1 adopts a cystine-knot fold. Transcriptome analyses suggested that roseltides are bioprocessed by asparagine endopeptidases from a three-domain precursor. The cystine-knot structure of roseltide rT1 confers its high resistance against degradation by endopeptidases, 0.2 N HCl, and human serum. Roseltide rT1 was shown to inhibit human neutrophil elastase using enzymatic and pull-down assays. Additionally, roseltide rT1 ameliorates neutrophil elastase-stimulated cAMP accumulation in vitro. Taken together, our findings demonstrate that roseltide rT1 is a novel knottin-type neutrophil elastase inhibitor with therapeutic potential for neutrophil elastase associated diseases. Identification and Characterization of Roseltide, a Knottin-type Neutrophil Elastase Inhibitor Derived from Hibiscus sabdariffa.,Loo S, Kam A, Xiao T, Nguyen GK, Liu CF, Tam JP Sci Rep. 2016 Dec 19;6:39401. doi: 10.1038/srep39401. PMID:27991569[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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