A. Molecular surface representation of the 3D models. (a) Nucleotide-bound model built with the SAV1866 template. (b) Nucleotide-bound model built with the S. typhimurium MsbA template. (c) Closed and (d) Open nucleotide-free models built with the V. cholerae MsbA and the E. coli MsbA templates respectively. The surface of hydrophobic residues (Ala, Leu, Val, Ile, Pro, Phe and Met) are colored in yellow. Other residues are colored in blue. The two red lines indicate the position of the lipid polar heads in the cellular membrane. B. View of a nucleotide-bound conformation of P-gp. The N-terminal half is highlighted: the three extracellular loops (ECL) are colored in pink (ECL1 is truncated (see text)), the two long intracellular loops are colored in yellow with the small coupling helices in pale green. The 6 trans-membrane helices are colored in blue (TM1), red (TM2), gray (TM3), orange (TM4), cyan (TM5) and green (TM6) and the nucleotide binding domain (NBD) is colored in magenta. The intracellular segment of TM1 and TM6 are depicted in light blue. All these segments are labeled from the N-terminus to the C-terminus.