title: A cactus-derived toxin-like cystine knot Peptide with selective antimicrobial activity.
abstract: Naturally occurring cystine knot peptides show a wide range of biological activity, and as they have inherent stability they represent potential scaffolds for peptide-based drug design and biomolecular engineering. Here we report the discovery, sequencing, chemical synthesis, three-dimensional solution structure determination and bioactivity of the first cystine knot peptide from Cactaceae (cactus) family: Ep-AMP1 from Echinopsis pachanoi. The structure of Ep-AMP1 (35 amino acids) conforms to that of the inhibitor cystine knot (or knottin) family but represents a novel diverse sequence; its activity was more than 500 times higher against bacterial than against eukaryotic cells. Rapid bactericidal action and liposome leakage implicate membrane permeabilisation as the mechanism of action. Sequence homology places Ec-AMP1 in the plant C6-type of antimicrobial peptides, but the three dimensional structure is highly similar to that of a spider neurotoxin.
authors.affiliation: Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, 75123 Uppsala (Sweden); Department of Pharmaceutical Chemistry, School of Pharmacy, Addis Ababa University, Box 1176, Addis Ababa (Ethiopia).
authors.forename: Teshome L
authors.initials: TL
authors.lastname: Aboye
authors.forename: Adam A
authors.initials: AA
authors.lastname: Strömstedt
authors.forename: Sunithi
authors.initials: S
authors.lastname: Gunasekera
authors.forename: Jan G
authors.initials: JG
authors.lastname: Bruhn
authors.forename: Hesham
authors.initials: H
authors.lastname: El-Seedi
authors.forename: K Johan
authors.initials: KJ
authors.lastname: Rosengren
authors.forename: Ulf
authors.initials: U
authors.lastname: Göransson
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D029421:Cactaceae / Q000737:chemistry*; D002176:Candida albicans / Q000187:drug effects; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D003553:Cystine / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011487:Protein Conformation; D017421:Sequence Analysis
chemical_list: D000890:Anti-Infective Agents; D004220:Disulfides; D010455:Peptides; D003553:Cystine
keywords: C6-type AMP; Cactaceae; antibiotics; cystine knot; drug discovery; plant antimicrobial peptide