The translocation of many drugs and endogenous molecules across the cellular and organelle membranes is facilitated by transporter proteins. Among these, the organic cation transporter OCT1 (SLC22A1), a member of the SLC22 family, is predominantly expressed in the liver and was first identified in 1994. OCT1 has been characterized as a key hepatic transporter for various pharmacologically significant agents, including metformin, the anti-cancer drug oxaliplatin and morphine. OCT1 is also known to transport thiamine with high capacity, thereby regulating hepatic steatosis by modulating cellular energy status7, with additional roles as a neurotransmitter transporter that controls levels of circulating catecholamines. The function of hOCT1 impacts the pharmacokinetics of many drugs and pharmacogenomic studies have shown genetic polymorphisms impacting hOCT1 activity can modify drug effects, sometimes resulting in adverse effects. Here you can see a cryoEM structure of the human hOCT1 in complex with metformin in outward occluded conformation, as a part of a bigger study published by Zhang and coworkers in Nat. Comms. (doi.org/10.1038/s41421-024-00664-1, PDB code: 8JTT).

Structure rendered with @proteinimaging, post-processed with @stylar.ai_official and depicted with @corelphotopaint.

#molecularart ... #receptor ... #membrane ... #cryoem ... #hOCT1 ... #translocation