Fig. 8
Localization of the functional amino acid substitutions within the OCT1 protein. a Schematic representation of the secondary structure of OCT1 with the positions of the amino acid substitutions causing strong changes in OCT1 activity indicated. Substitutions leading to substrate-specific loss of activity are shown in orange, substitutions leading to partial, but substrate-overarching, loss of activity in red, substitutions leading to complete substrate-overarching loss of activity in dark red, and substitutions leading to gain of function are shown in green. The amino acids threonine516 and lysine 517, which are assumed to be involved in interaction with serine401 (see below), are shown in gray. Potential phosphorylation (P) and glycosylation (ψ) sites are indicated as they were predicted by Zhang et al. [6]. b A 3D model of the OCT1 protein with the position of the Gly401Ser polymorphism highlighted. Represented is a homology model of the inward-facing conformation of OCT1 (Model-ID Q9NQD4, ModBase [51]) which was visualized using PyMol software version 1.3 (Schrödinger, LLC, München, Germany). The model is based on homology with lactose permease LacY of Escherichia coli (PDB number 1pv6). Gly401Ser substitution is shown as a red sphere. Transmembrane helices TMH8, TMH9 and TMH12, the N terminus and C terminus are indicated. c A detailed representation of the region of the Gly401Ser substitution indicating a potential hydrogen bond between the hydroxyl oxygen of serine401 and the carbonyl oxygen of threonine516. A hydrogen bond could also be established between the hydroxyl oxygen of serine401 and the side chain amino group of lysine517 assuming other rotational conformations for that side chains are allowed. The position of serine401, threonine516 and lysine517 are shown in details. Oxygen atoms are depicted in red and nitrogen atoms in blue