Identification of putative steroid-binding sites in human ABCB1 and ABCG2.

Homology modelling was used to generate three-dimensional structures of the nucleotide-binding domains (NBDs) of human ABCB1 and ABCG2. Interactions between a series of steroidal ligands and transporter NBDs were investigated using an in silico docking approach. C-terminal ABCB1 NBD (ABCB1 NBD2) was predicted to bind steroids within a cavity formed partly by the P-Loop, Tyr1044 and Ile1050. The P-Loop within ABCG2 NBD was also predicted to be involved in steroid binding. No overlap between ATP- and RU-486-binding sites was predicted in either NBD, though overlaps between ATP- and steroid-binding sites were predicted in the vicinity of the P-Loop in both nucleotide-binding domains.