FIGURE 6.

Sugar permeation across LacY. Superimposed on LacY are eight snapshots, taken from simulation LacY(269^H/325⁻), of lactose shown alternately in light and dark. The C-domain is shown in a green surface representation; the N-domain is drawn only partially, for clarity, and is shown in brown ribbon representation. Key N-domain residues, shown in stick representation are Ile-40, Phe-27, Arg-144, Glu-126, Glu-130, and Arg-134. The latter four residues form an ionic ladder stabilizing lactose during its passage across the constriction within the cytoplasmic half-channel as defined by Phe-334 and Tyr-350 (see text). Passage across this region is shown in detail in the upper right inset with Phe-334 (almost hidden, not annotated) and Tyr-350 displayed in van der Waals representation. This region remains fairly hydrated during sugar passage. Phe-27 and Ile-40 of the N-domain interact with lactose within the binding cavity and within the tight periplasmic constriction, respectively. Passage across the latter, also defined by Asn-245, is shown in detail in the lower right inset with Ile-40 (almost hidden) and Asn-245 displayed in van der Waals representation. This region is poorly hydrated during sugar passage. Two key C-domain residues, shown in stick representation, are Tyr-350 and Glu-269 (protonated). Within the binding cavity, lactose engages in interactions with other key residues (Trp-151, Asp-237, Asp-240, His-322) omitted for visual clarity (see text, Fig. 2, and Table 1); within the cytoplasmic constriction region lactose engages in hydrophobic interactions with aromatic residues (Phe-30, Phe-49, Phe-261, all omitted for visual clarity, see text and Table 1). Absolute conformational changes of cytoplasmic and periplasmic half-channels are schematically illustrated by lateral arrows. The channel diameter widens in response to sugar passage across the latter half-channel (cf. Fig. 4).