Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Mechanisms of transport and analgesic compounds recognition by glycine transporter 2.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 122, Issue 48, Page e2506722122, Year 2025
Publish date	Dec 2, 2025
Authors	Yuhang Wang / Jiawei Su / Jun Zhao / Renjie Li / Qinru Bai / Hongyi Song / Yufei Meng / Qiao Ma / Yan Zhao /
PubMed Abstract	Glycine transporter 2 (GlyT2) regulates inhibitory glycinergic neurotransmission, and its inhibition potentiates glycinergic signaling, which is a promising strategy for managing neuropathic pain. ...Glycine transporter 2 (GlyT2) regulates inhibitory glycinergic neurotransmission, and its inhibition potentiates glycinergic signaling, which is a promising strategy for managing neuropathic pain. This study presents high-resolution structures of GlyT2 in its apo state and in complexes with the substrate glycine, analgesic inhibitors, captured in three functional states: outward-facing, occluded, and inward-facing. The glycine-bound structure reveals the binding mode of the substrate, Na and Cl. Specifically, we identified the Na3 binding site, offering fundamental insights into Na/Cl coupled substrate binding and conformational changes. Moreover, we clearly elucidate a previously unseen allosteric binding pocket for the lipid-based oleoyl-D-lysine, which acts as a wedge to stabilize GlyT2 in the outward-facing conformation and prevents its transition. Furthermore, the complex structures with small compounds ALX1393, opiranserin, and ORG25543 reveal their competitive and allosteric inhibition mechanisms. Overall, our study provides a solid foundation for understanding glycine reuptake mechanisms and developing effective and safer analgesic agents.
External links	Proc Natl Acad Sci U S A / PubMed:41284875 / PubMed Central
Methods	EM (single particle)
Resolution	2.8 - 3.8 Å
Structure data	62420 9km2 EMDB-62420, PDB-9km2: Cryo-EM structure of apo glycine transporter 2 in inward-facing state Method: EM (single particle) / Resolution: 3.8 Å 62421 9km3 EMDB-62421, PDB-9km3: Cryo-EM structure of glycine transporter 2 in complex with substrate glycine Method: EM (single particle) / Resolution: 2.9 Å 62422 9km4 EMDB-62422, PDB-9km4: Cryo-EM structure of glycine transporter 2 in complex with oleoyl-D-lysine Method: EM (single particle) / Resolution: 3.2 Å 62423 9km5 EMDB-62423, PDB-9km5: Cryo-EM structure of Xenopus tropicalis glycine transporter 2 in complex with ALX1393 Method: EM (single particle) / Resolution: 3.5 Å 62424 9km7 EMDB-62424, PDB-9km7: Cryo-EM structure of glycine transporter 2 in complex with ORG25543 Method: EM (single particle) / Resolution: 2.8 Å 62425 9km8 EMDB-62425, PDB-9km8: Cryo-EM structure of Xenopus tropicalis glycine transporter 2 in complex with VVZ149 Method: EM (single particle) / Resolution: 3.5 Å
Chemicals	ChemComp-CLR: CHOLESTEROL ChemComp-GLY: GLYCINE ChemComp-NA: Unknown entry ChemComp-CL: Unknown entry ChemComp-HOH: WATER ChemComp-DLY: D-LYSINE ChemComp-OLA: OLEIC ACID PDB-1ez0: CRYSTAL STRUCTURE OF THE NADP+ DEPENDENT ALDEHYDE DEHYDROGENASE FROM VIBRIO HARVEYI. PDB-1ef1: CRYSTAL STRUCTURE OF THE MOESIN FERM DOMAIN/TAIL DOMAIN COMPLEX PDB-1ef3: FIDARESTAT BOUND TO HUMAN ALDOSE REDUCTASE
Source	xenopus tropicalis (tropical clawed frog)
Keywords	MEMBRANE PROTEIN / GLYT2; PROTEIN STRUCTURE