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 Ala(4)-His(7) and Lys(11)-Ser(20). 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.
Keywords: NMR; antimicrobial peptide; head-to-tail cyclization; histatin-5; molecular dynamics simulations.
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