Effect of head-to-tail cyclization on conformation of histatin-5

• Published in: Journal of peptide science 2014-12, Vol.20 (12), p.952-957
• Main Authors: Sikorska, Emilia, Kamysz, Elżbieta
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; antimicrobial peptide; Candida albicans; Cyclization; head-to-tail cyclization; histatin-5; Histatins - chemistry; Molecular Dynamics Simulation; molecular dynamics simulations; Molecular Sequence Data; NMR; Nuclear Magnetic Resonance, Biomolecular; Peptides; Protein Conformation
• ISSN: 1075-2617; 1099-1387
• DOI: 10.1002/psc.2707

Histatin‐5 (Hst‐5, DSHAKRHHGYKRKFHEKHHSHRGY) is a member of a histidine‐rich peptide family secreted by major salivary glands, exhibiting high fungicidal activity against Candida albicans. In the present work, we demonstrate the 3D structure of the head‐to‐tail cyclic variant of Hst‐5 in TFE solution determined using NMR spectroscopy and molecular dynamics simulations. The cyclic histatin‐5 reveals a helix‐loop‐helix motif with α‐helices at positions Ala4‐His7 and Lys11‐Ser20. Both helical segments are arranged relative to each other at an angle of ca. 142°. The head‐to‐tail cyclization increases amphipathicity of the peptide, this, however, does not affect its antimicrobial potency. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. Histatin‐5 is a member of a histidine‐rich peptide family secreted by major salivary glands, exhibiting high fungicidal activity against Candida albicans. We demonstrate the 3D structure of the head‐to‐tail cyclic variant of Hst‐5 in TFE solution determined using NMR spectroscopy and molecular dynamics simulations. The cyclic histatin‐5 reveals a helix‐loop‐helix motif with α‐helices at positions Ala4‐His7 and Lys11‐Ser20. The head‐to‐tail cyclization increases amphipathicity of the peptide, this, however, does not affect its antimicrobial potency.