Putative substrate-binding site in lac permease. Helices IV (white) and V (green) are shown with Glu-126 (green), Arg-144 (white), Met-145 (orange), and Cys-148 (yellow). The galactosyl and glucosyl moieties of lactose are in light and dark blue, respectively. As indicated, one of the guanidino NH2 groups of Arg-144 interacts with the hydroxyl group at the C4 and/or C3 positions of the galactosyl moiety, and the other guanidino NH2 group interacts with Glu-126, which may also interact with the C6-OH of the galactosyl moiety. Cys-148 interacts weakly and hydrophobically with the galactosyl moiety, and Met-145 interacts even more weakly with the glucosyl part of lactose.