The crystal structure of the lipoaminopeptaibol helioferin, an antibiotic peptide from Mycogone rosea

• Published in: Acta crystallographica. Section D, Biological crystallography. Vol. 74; no. Pt 4; pp. 315 - 320
• Main Authors: Gessmann, Renate, Brückner, Hans, Berg, Albrecht, Petratos, Kyriacos
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2018
• Subjects: Acids; Aliphatic compounds; Anions; Anti-Bacterial Agents - chemistry; Antibiotics; Biological activity; Chains; Conformation; Crystal structure; Crystallization; Crystallography, X-Ray; Ethanol; Fungal Proteins - chemistry; Fungi - chemistry; Helices; Homology; Hydrogen Bonding; Hydrogen bonds; Hydrophobic and Hydrophilic Interactions; Leucinostatin; Molecular chains; Mycogone rosea; Octanoic acid; Peptides; Peptides - chemistry; Rods; Static Electricity; tight crystal packing; peptaibiotics; peptaibols; antibiotic peptides; helioferin; Mycogone rosea; lipoaminopeptaibols
• ISSN: 0907-4449; 2059-7983; 1399-0047
• DOI: 10.1107/S2059798318001857

The crystal structure of the natural nonapeptide antibiotic helioferin has been determined and refined to 0.9 Å resolution. Helioferin consists of helioferin A and B, which contain 2-(2'-aminopropyl)aminoethanol (Apae) and 2-[(2'-aminopropyl)methylamino]ethanol (Amae) at their respective alkanolamine termini. In addition, helioferin contains the unusual amino-acid residues α-aminoisobutyric acid (Aib) and (2S,4S,6S)-2-amino-6-hydroxy-4-methyl-8-oxodecanoic acid (Ahmod). The amino-terminus is capped with 2-methyl-n-1-octanoic acid (M8a). The peptide crystallizes with a 1:1 molar ratio of helioferin A and B in the monoclinic space group C2, with unit-cell parameters a = 34.711, b = 10.886, c = 17.150 Å, β = 93.05°. The peptide backbone folds in a regular right-handed α-helical conformation, with eight intramolecular hydrogen bonds, all but one forming 5→1 interactions. The two aliphatic chains of the fatty-acyl (M8a) and the second residue (Ahmod) extend out of the α-helical structure in opposite directions and lead to a corkscrew-like shape of the peptide molecule. Halogen anions (Cl and F ) have been co-crystallized with the peptide molecules, implying a positive charge at the aminoalcohol end of the peptide. In the tightly packed crystal the helices are linked head to tail via the anions by electrostatic, hydrogen-bond and van der Waals interactions, forming continuous helical rods. Two nonparallel rods (forming an angle of 118°) interact directly via hydrogen bonds and via the anions, forming a double layer. Successive double layers are held together only via van der Waals contacts. The helical axes of successive double layers are also related by an angle of 118°. The structure of helioferin reported here and the previously determined structure of the homologous leucinostatin A have a total straight length of about 21 Å, indicating a different membrane-modifying bioactivity from that of long-chain, amphiphilic peptaibols.