9R0O
Cryo-EM structure of rat SLCO2A1 bound to tolcapone.
Summary for 9R0O
| Entry DOI | 10.2210/pdb9r0o/pdb |
| EMDB information | 53486 |
| Descriptor | Solute carrier organic anion transporter family member 2A1, Tolcapone (2 entities in total) |
| Functional Keywords | oatp2a1, plasma membrane localised, prostaglandin transporter, pgt, major facilitator superfamily., membrane protein |
| Biological source | Rattus norvegicus (Norway rat) |
| Total number of polymer chains | 1 |
| Total formula weight | 72888.36 |
| Authors | Deme, J.C.,Joshi, C.,Lea, S.M.,Newstead, S. (deposition date: 2025-04-24, release date: 2026-02-11, Last modification date: 2026-04-01) |
| Primary citation | Joshi, C.,Deme, J.C.,Nakamura, Y.,Hsu, W.T.,Goult, J.D.,Kato, T.,Parker, J.L.,Biggin, P.C.,Lea, S.M.,Nakanishi, T.,Newstead, S. Structural basis for prostaglandin and drug transport via SLCO2A1. Nat Commun, 17:-, 2026 Cited by PubMed Abstract: Organic anion-transporting polypeptide transporters (SLCO/OATPs) function as cellular gatekeepers, regulating intestinal absorption, hepatic and renal clearance, and the tissue distribution of drugs and metabolites in the human body. However, the mechanisms underlying substrate selection within the SLCO superfamily remain unclear, hampering efforts to rationalize the interaction of drugs and metabolites with these transporters. SLCO2A1 (also known as OATP2A1) is responsible for the distribution of eicosanoids, including prostaglandins (PGs) and thromboxanes, throughout the body, in addition to several families of nonsteroidal anti-inflammatory drugs (NSAIDs). Here, we present cryogenic electron microscopy structures of SLCO2A1 bound to endogenous PGs and to four widely prescribed medications for treating inflammation, chronic asthma, and Parkinson's disease (PD). Complementary molecular dynamics and in vivo cellular assays elucidate the molecular basis for PG and drug recognition. Our study reports essential mechanistic details that underpin substrate selection and subfamily adaptation within the broader SLCO superfamily of drug and metabolite transporters. PubMed: 41862483DOI: 10.1038/s41467-026-70227-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
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