Conformation of a 16-residue zervamicin IIA analog peptide containing three different structural features: 3₁₀-helix, α-helix, and β-bend ribbon

Abstract

Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib- Pro-Ala-Aib-Pro-Aib-Pro-Phe-OMe (where Boc is t-butoxycarbonyl and Aib is a-aminoisobutyric acid), a synthetic apolar analog of the membrane-active fungal peptide antibiotic zervamycin IIA, crystallizes in space group P1 with Z = 1 and cell parameters a = 9.086 ± 0.002 A:, b = 10.410 ± 0.002 A, c = 28.188 ± 0.004 A, α = 86.13 ± 0.01°, β = 87.90 ± 0.01°, and γ = 89.27 ± 0.01°; overall agreement factor R = 7.3% for 7180 data (F_o > 3σ) and 0.91-A resolution. The peptide backbone makes a continuous spiral that begins as a 31₀-helix at the N-terminus, changes to an α-helix for two turns, and ends in a spiral of three β-bends in a ribbon. Each of the β-bends contains a proline residue at one of the corners. The torsion angles φ_i range from -51° to -91° (average value -64°), and the torsion angles ψ_i range from -1° to -46° (average value -31°). There are 10 intramolecular NH-..OC hydrogen bonds in the helix and two direct head-to-tail hydrogen bonds between successive molecules. Two H₂0 and two CH₃OH solvent molecules fill additional space with appropriate hydrogen bonding in the head-to-tail region, and two additional H₂0 molecules form hydrogen bonds with carbonyl oxygens near the curve in the helix at Pro-10. Since there is only one peptide molecule per cell in space group P1, the molecules repeat only by translation, and consequently the helices pack parallel to each other.