dc.contributor.authorNguyen, Phuong Quoc Thuc
dc.contributor.authorOoi, Justin Seng Geap
dc.contributor.authorNguyen, Ngan Thi Kim
dc.contributor.authorWang, Shujing
dc.contributor.authorHuang, Mei
dc.contributor.authorLiu, Ding Xiang
dc.contributor.authorTam, James P.
dc.date.accessioned2018-09-20T03:57:48Z
dc.date.available2018-09-20T03:57:48Z
dc.date.issued2015
dc.identifier.citationNguyen, P. Q. T., Ooi, J. S. G., Nguyen, N. T. K., Wang, S., Huang, M., Liu, D. X., & Tam, J. P. (2015). Antiviral cystine knot α-amylase inhibitors from alstonia scholaris. Journal of Biological Chemistry, 290(52), 31138-31150. doi:10.1074/jbc.M115.654855en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://hdl.handle.net/10220/46053
dc.description.abstractCystine knot α-amylase inhibitors are cysteine-rich, proline-rich peptides found in the Amaranthaceae and Apocynaceae plant species. They are characterized by a pseudocyclic backbone with two to four prolines and three disulfides arranged in a knotted motif. Similar to other knottins, cystine knot α-amylase inhibitors are highly resistant to degradation by heat and protease treatments. Thus far, only the α-amylase inhibition activity has been described for members of this family. Here, we show that cystine knot α-amylase inhibitors named alstotides discovered from the Alstonia scholaris plant of the Apocynaceae family display antiviral activity. The alstotides (As1–As4) were characterized by both proteomic and genomic methods. All four alsotides are novel, heat-stable and enzyme-stable and contain 30 residues. NMR determination of As1 and As4 structures reveals their conserved structural fold and the presence of one or more cis-proline bonds, characteristics shared by other cystine knot α-amylase inhibitors. Genomic analysis showed that they contain a three-domain precursor, an arrangement common to other knottins. We also showed that alstotides are antiviral and cell-permeable to inhibit the early phase of infectious bronchitis virus and Dengue infection, in addition to their ability to inhibit α-amylase. Taken together, our results expand membership of cystine knot α-amylase inhibitors in the Apocynaceae family and their bioactivity, functional promiscuity that could be exploited as leads in developing therapeutics.en_US
dc.description.sponsorshipNRF (Natl Research Foundation, S’pore)en_US
dc.format.extent13 p.en_US
dc.language.isoenen_US
dc.relation.ispartofseriesJournal of Biological Chemistryen_US
dc.rights© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. This paper was published in Journal of Biological Chemistry and is made available as an electronic reprint (preprint) with permission of The American Society for Biochemistry and Molecular Biology, Inc. The published version is available at: [http://dx.doi.org/10.1074/jbc.M115.654855]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.en_US
dc.subjectAntiviral Agenten_US
dc.subjectCysteine-mediated Cross-linkingen_US
dc.subjectDRNTU::Science::Biological sciencesen_US
dc.titleAntiviral cystine knot α-amylase inhibitors from alstonia scholarisen_US
dc.typeJournal Article
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M115.654855
dc.description.versionPublished versionen_US


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