2ncu
From Proteopedia
(Difference between revisions)
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/HEP2_HUMAN HEP2_HUMAN]] Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT-III). Also inhibits chymotrypsin, but in a glycosaminoglycan-independent manner.<ref>PMID:1939083</ref> Peptides at the N-terminal of HC-II have chemotactic activity for both monocytes and neutrophils.<ref>PMID:1939083</ref> | [[http://www.uniprot.org/uniprot/HEP2_HUMAN HEP2_HUMAN]] Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT-III). Also inhibits chymotrypsin, but in a glycosaminoglycan-independent manner.<ref>PMID:1939083</ref> Peptides at the N-terminal of HC-II have chemotactic activity for both monocytes and neutrophils.<ref>PMID:1939083</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The objective of the present study is the investigation of possibilities for boosting peptide anti-inflammatory effects by tryptophan end-tagging, including identification of underlying mechanisms for this. In doing so, effects of tryptophan end-tagging of KYE21 (KYEITTIHNLFRKLTHRLFRR), a peptide derived from heparin co-factor II, on membrane and lipopolysaccharide (LPS) interactions were investigated by ellipsometry, NMR, fluorescence spectroscopy, and circular dichroism measurements. Through its N-terminal W stretch, WWWKYE21 displays higher membrane binding, liposome rupture, and bacterial killing than unmodified KYE21. Analogously, W-tagging promotes binding to E. coli LPS and to its endotoxic lipid A moiety. Furthermore, WWWKYE21 causes more stable peptide/LPS complexes than KYE21, as evidenced by detailed NMR studies, adopting a pronounced helical conformation, with a large hydrophobic surface at the N-terminus due to the presence of W-residues, and a flexible C-terminus due to presence of several positively charged arginine residues. Mirroring its increased affinity for LPS and lipid A, WWWKYE21 displays strongly increased anti-inflammatory effect due to a combination of direct lipid A binding, peptide-induced charge reversal of cell membranes for LPS scavenging, and peptide-induced fragmentation of LPS aggregates for improved phagocytosis. Importantly, potent anti-inflammatory effects were observed at low cell toxicity, demonstrated for both monocytes and erythrocytes. | ||
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| + | Tryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects.,Singh S, Datta A, Schmidtchen A, Bhunia A, Malmsten M Sci Rep. 2017 Mar 16;7(1):212. doi: 10.1038/s41598-017-00188-7. PMID:28303012<ref>PMID:28303012</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 2ncu" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 06:55, 29 March 2017
NMR structure of KYE21 in LPS micelles
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