{"refrec":{"BRefID":280628,"RR":"<b>García-Fernández, R.; Peigneur, S.; Pons, T.; Alvarez, C.; González, L.; Chávez, M.A.; Tytgat, J.</b> (2016). The Kunitz-type protein ShPI-1 inhibits serine proteases and voltage-gated potassium channels. <i>Toxins 8(4)</i>: 110. <a href=\"http://dx.doi.org/10.3390/toxins8040110\" target=\"_blank\">dx.doi.org/10.3390/toxins8040110</a>","BEntID":272647,"PublicFlag":1,"CheckedFlag":1,"wosflag":1,"vabbflag":1,"RefStringPartII":". <i>Toxins 8(4)</i>: 110. <a href=\"https://dx.doi.org/10.3390/toxins8040110\" target=\"_blank\">https://dx.doi.org/10.3390/toxins8040110</a>","DocTypID":8,"DocType":"Journal article","MarineFlag":1,"FreshFlag":0,"BrackishFlag":0,"TerrestrialFlag":0,"Authorstring":"García-Fernández, R.; Peigneur, S.; Pons, T.; Alvarez, C.; González, L.; Chávez, M.A.; Tytgat, J.","OrigTitleTranslFlag":0,"Authorstringtrunc":"García-Fernández, R. <i>et al.</i>","Englishabstract":"The bovine pancreatic trypsin inhibitor (BPTI)-Kunitz-type protein ShPI-1 (UniProt: P31713) is the major protease inhibitor from the sea anemone <i>Stichodactyla helianthus</i>. This molecule is used in biotechnology and has biomedical potential related to its anti-parasitic effect. A pseudo wild-type variant, <i>r</i>ShPI-1A, with additional residues at the <i>N</i>- and <i>C</i>-terminal, has a similar three-dimensional structure and comparable trypsin inhibition strength. Further insights into the structure-function relationship of <i>r</i>ShPI-1A are required in order to obtain a better understanding of the mechanism of action of this sea anemone peptide. Using enzyme kinetics, we now investigated its activity against other serine proteases. Considering previous reports of bifunctional Kunitz-type proteins from anemones, we also studied the effect of <i>r</i>ShPI-1A on voltage-gated potassium (Kv) channels. <i>r</i>ShPI-1A binds Kv1.1, Kv1.2, and Kv1.6 channels with IC<sub>50</sub> values in the nM range. Hence, ShPI-1 is the first member of the sea anemone type 2 potassium channel toxins family with tight-binding potency against several proteases and different Kv1 channels. In depth sequence analysis and structural comparison of ShPI-1 with similar protease inhibitors and Kv channel toxins showed apparent non-sequence conservation for known key residues. However, we detected two subtle patterns of coordinated amino acid substitutions flanking the conserved cysteine residues at the <i>N</i>- and <i>C</i>-terminal ends.","AbstractOtherLang":null,"BibLvlCode":"AS","StandardTitle":"The Kunitz-type protein ShPI-1 inhibits serine proteases and voltage-gated potassium channels","OrigTitleLangCode":"en","OrigTitleLangCodeExtended":"eng","OrigTitleLangID":15,"DateLastModified":{"date":"2024-12-10 01:33:17.368041","timezone_type":1,"timezone":"+01:00"},"UserAccessRight":null,"UserAccID":null,"AuthorKeywords":"protease inhibitor; Kv channel inhibitor; sea anemone; toxin;Kunitz-type protein","OtherDescriptors":null,"Notes":null,"AnaPub":2016,"MonPub":null,"DateUpdate":"2016-10-18","DateCreate":"2016-10-09","SecASFANote":null,"ConfID":null,"PeerRev":1,"VlizCoreFlag":1,"WoScode":"WOS:000375861700025","VABBcode":null,"OpenAcc":1,"DOI":"10.3390/toxins8040110"},"refs":null,"anarec":{"AnaID":280628,"PubliDate":2016,"Pagination":"110","XtraPublOfAnaID":null,"ISBN":null,"Volume":"8","Issue":"4","BRefMon":null,"BRefMonRR":null,"BRefXtra":null,"BRefXtraRR":null,"SerBRefID":197331,"SerRR":"Toxins. 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