Conformation of the flexible bent helix of Leu1-zervamicin in crystal C and a possible gating action for ion passage.

The membrane channel-forming polypeptide, Leu1-zervamicin, Ac-Leu-Ile-Gln-Iva-Ile5-Thr-Aib-Leu-Aib-Hyp10-Gln-Aib-Hyp-Aib-P ro15-Phol (Aib: alpha-aminoisobutyric acid; Iva: isovaline; Hyp: 4-hydroxyproline; Phol: phenylalininol) has been analyzed by x-ray diffraction in a third crystal form. Although the bent helix is quite similar to the conformations found in crystals A and B, the amount of bending is more severe with a bending angle approximately 47 degrees. The water channel formed by the convex polar faces of neighboring helices is larger at the mouth than in crystals A and B, and the water sites have become disordered. The channel is interrupted in the middle by a hydrogen bond between the OH of Hyp (10) and the NH2 of the Gln(11) of a neighboring molecule. The side chain of Gln(11) is wrapped around the helix backbone in an unusual fashion in order that it can augment the polar side of the helix. In the present crystal C there appears to be an additional conformation for the Gln(11) side chain (with approximately 20% occupancy) that opens the channel for possible ion passage. Structure parameters for C85H140N18O22.xH2O.C2H5OH are space group P2(1)2(1)2(1), a = 10.337(2) A, b = 28.387(7) A, c = 39.864(11) A, Z = 4, agreement factor R = 12.99% for 3250 data observed > 3 sigma (F), resolution = 1.2 A.