9V3ZSummary for 9V3Z
| Entry DOI | 10.2210/pdb9v3z/pdb |
| EMDB information | 64762 |
| Descriptor | Proton-coupled amino acid transporter 1, 2-acetamido-2-deoxy-beta-D-glucopyranose, (3S)-piperidine-3-carboxylic acid (3 entities in total) |
| Functional Keywords | lysosomal membrane protein npa, transport protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 53462.60 |
| Authors | |
| Primary citation | Yin, J.,Zhang, S.,Liu, C.,Xie, M.,Gao, Y.,Chen, M.,Wang, Y.,Chen, M.,Fan, H.,Yang, Z.,Li, H.,Liang, L.,Zhou, B.,Chen, X.,Yang, M. Substrate recognition and transport mechanism of the human proton-coupled amino-acid transporter 1 (SLC36A1). Nat Commun, 2026 Cited by PubMed Abstract: The proton-coupled amino-acid transporter SLC36A1 (hPAT1) is an atypical H⁺-driven carrier and mediates the intestinal absorption of a wide array of zwitterionic amino-acid analogs, including many compounds with central nervous-system (CNS) activity, as well as the activation of the mTORC1 pathway and the export of amino acids from lysosomes, thereby maintaining cellular amino-acid homeostasis. Here, we present the cryo-EM structures of a member of the SLC36 family, hPAT1, in its apo state and in complex with three chemically distinct substrates, including the α-amino acid D-serine, the β-amino acid nipecotic acid, and the heterocyclic drug D-cycloserine, at resolutions of 3.4-3.5 Å. Despite their chemical diversity, all ligands adopt a spatially convergent binding mode, elucidating the structural basis for PAT1's broad substrate promiscuity. In addition, we identify E270 as a potential proton-binding site. Together, these findings provide structural insights into the molecular mechanism of proton-coupled amino acid transport. Notably, the cryo-EM structure of PAT1 bound to D-cycloserine illustrates a viable oral CNS drug delivery strategy: exploiting polar scaffolds to achieve transporter-mediated intestinal absorption and blood-brain barrier penetration without relying on high lipophilicity. PubMed: 42414312DOI: 10.1038/s41467-026-75306-z PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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