| RRC ID |
87214
|
| 著者 |
Joshi C, Deme JC, Nakamura Y, Hsu WT, Goult JD, Kato T, Parker JL, Biggin PC, Lea SM, Nakanishi T, Newstead S.
|
| タイトル |
Structural basis for prostaglandin and drug transport via SLCO2A1.
|
| ジャーナル |
Nat Commun
|
| 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.
|
| 巻・号 |
17(1)
|
| 公開日 |
2026-3-20
|
| DOI |
10.1038/s41467-026-70227-3
|
| PII |
10.1038/s41467-026-70227-3
|
| PMID |
41862483
|
| PMC |
PMC13005041
|
| MeSH |
Animals
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / metabolism
Biological Transport
Cryoelectron Microscopy
HEK293 Cells
Humans
Molecular Dynamics Simulation
Organic Anion Transporters* / chemistry
Organic Anion Transporters* / genetics
Organic Anion Transporters* / metabolism
Organic Anion Transporters* / ultrastructure
Prostaglandins* / chemistry
Prostaglandins* / metabolism
|
| IF |
12.121
|
| リソース情報 |
| ヒト・動物細胞 |
293(RCB1637) |
