Solute carrier organic anion transporter 1B subfamily of the Major Facilitator Superfamily of transporters
The Solute carrier organic anion transporter 1B (SLCO1B), also called organic anion-transporting polypeptide 1B (OATP1B), subfamily is composed of two human proteins, OATP1B1 (encoded by SLCO1B1) and OATP1B3 (encoded by SLCO1B3), and one rodent member, OATP1B2 (encoded by Slco1b2). OATP1B1 and OATP1B3 are almost exclusively expressed on the basal side of hepatocytes in normal human organs. They both can accept a wide variety of structurally-unrelated compounds as substrates including clinically-important drugs such as hydroxymethylglutaryl (HMG)-CoA reductase inhibitors (statins), angiotensin II receptor blockers (sartans), angiotensin converting enzyme (ACE) inhibitors, and anti-diabetes drugs (glinides). Loss-of-function mutations in both SLCO1B1 and SLCO1B3 genes result in the Rotor syndrome, a hereditary hyperbilirubinemia. The SLCO1B/OATP1B subfamily belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Feature 1:putative chemical substrate binding pocket [chemical binding site]
Evidence:
Comment:based on the structures of MFS transporters with bound substrates, substrate analogs, and/or inhibitors
Comment:since MFS proteins facilitate the transport of many different substrates including ions, sugar phosphates, drugs, neurotransmitters, nucleosides, amino acids, and peptides, the residues involved in substrate binding may not be strictly conserved among superfamily members
Comment:the substrate binding site or translocation pore has access to both sides of the membrane in an alternating fashion through a conformational change of the MFS transporter