IMBB-FORTH, N. Plastira 100, 70013 Heraklion, Greece.
Research Center for BioSystems, Land Use and Nutrition (IFZ), Institute of Nutritional Science, Department of Food Sciences, Heinrich-Buff-Ring 26-32, 65392 Giessen, Germany.
Acta Crystallogr D Struct Biol. 2018 Apr 1;74(Pt 4):315-320. doi: 10.1107/S2059798318001857. Epub 2018 Apr 3.
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.
天然九肽抗生素海利弗林的晶体结构已被确定，并精修至 0.9 Å 分辨率。海利弗林由海利弗林 A 和 B 组成，它们在各自的醇胺末端分别含有 2-(2'-氨基丙基)氨基乙醇 (Apae) 和 2-[(2'-氨基丙基)甲基氨基]乙醇 (Amae)。此外，海利弗林还含有不常见的氨基酸残基 α-氨基异丁酸 (Aib) 和 (2S,4S,6S)-2-氨基-6-羟基-4-甲基-8-氧代癸酸 (Ahmod)。其氨基末端用 2-甲基-n-1-辛酸 (M8a) 封端。该肽以 1:1 的摩尔比与海利弗林 A 和 B 结晶，属于单斜空间群 C2，晶胞参数为 a = 34.711, b = 10.886, c = 17.150 Å, β = 93.05°。肽骨架折叠成规则的右手α-螺旋构象，有 8 个分子内氢键，除一个氢键外，其余均形成 5→1 相互作用。脂肪酸酰基 (M8a) 和第二个残基 (Ahmod) 的两条脂肪链从α-螺旋结构中向相反方向延伸，导致肽分子呈螺旋状。卤素阴离子 (Cl 和 F) 与肽分子共结晶，表明肽分子氨基醇末端带正电荷。在紧密堆积的晶体中，通过静电、氢键和范德华相互作用，螺旋通过阴离子首尾相连，形成连续的螺旋棒。两个非平行的棒 (形成 118°的夹角) 通过氢键和阴离子直接相互作用，形成双层。相邻的双层仅通过范德华接触结合在一起。连续双层的螺旋轴之间也存在 118°的夹角。这里报道的海利弗林结构和以前确定的同源亮氨脂素 A 结构的总长度约为 21 Å，表明其具有不同于长链两亲性肽类的不同的膜修饰生物活性。
