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-Structure paper
タイトル | The substrate and inhibitor binding mechanism of polyspecific transporter OAT1 revealed by high-resolution cryo-EM. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 30, Issue 11, Page 1794-1805, Year 2023 |
掲載日 | 2023年10月16日 |
著者 | Tongyi Dou / Tengfei Lian / Shi Shu / Yi He / Jiansen Jiang / |
PubMed 要旨 | Organic anion transporters (OATs) of the SLC22 family have crucial roles in the transport of organic anions, including metabolites and therapeutic drugs, and in transporter-mediated drug-drug ...Organic anion transporters (OATs) of the SLC22 family have crucial roles in the transport of organic anions, including metabolites and therapeutic drugs, and in transporter-mediated drug-drug interactions. In the kidneys, OATs facilitate the elimination of metabolic waste products and xenobiotics. However, their transport activities can lead to the accumulation of certain toxic compounds within cells, causing kidney damage. Moreover, OATs are important drug targets, because their inhibition modulates the elimination or retention of substrates linked to diseases. Despite extensive research on OATs, the molecular basis of their substrate and inhibitor binding remains poorly understood. Here we report the cryo-EM structures of rat OAT1 (also known as SLC22A6) and its complexes with para-aminohippuric acid and probenecid at 2.1, 2.8 and 2.9 Å resolution, respectively. Our findings reveal a highly conserved substrate binding mechanism for SLC22 transporters, wherein four aromatic residues form a cage to accommodate the polyspecific binding of diverse compounds. |
リンク | Nat Struct Mol Biol / PubMed:37845412 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.05 - 2.86 Å |
構造データ | EMDB-40352, PDB-8sdu: EMDB-40354, PDB-8sdy: EMDB-40355, PDB-8sdz: EMDB-40948: RELION reconstruction of rat organic anion transporter 1 (OAT1) |
化合物 | ChemComp-HOH: ChemComp-ZWD: ChemComp-RTO: |
由来 |
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キーワード | TRANSPORT PROTEIN / organic anion transporter / OAT / SLC22 / drug transporter / PAH / probenecid |