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	Structure-guided development of a potent human BAT1 inhibitor effective in a mouse model of phenylketonuria.
Journal, issue, pages	Commun Biol, Year 2026
Publish date	Jun 25, 2026
Authors	Takuya Imazu / Tomoya Akashi / Masahiro Hiraizumi / Yosuke Inui / Wataru Sasaki / Tsuyoshi Takahashi / Hidenori Todoroki / Taichi Kumanomidou / Kazunori Yamada / Norie Fujikawa / Hiromi Hisano / Hidetsugu Asada / Tsukasa Kusakizako / Tomohiro Nishizawa / So Iwata / Osamu Nureki / Ikuko Miyaguchi /
PubMed Abstract	BAT1 (SLC6A19) is a neutral amino acid transporter mediating intestinal absorption and renal reuptake of amino acids, including phenylalanine (Phe). Inhibiting BAT1 enhances Phe excretion, offering a ...BAT1 (SLC6A19) is a neutral amino acid transporter mediating intestinal absorption and renal reuptake of amino acids, including phenylalanine (Phe). Inhibiting BAT1 enhances Phe excretion, offering a therapeutic strategy for phenylketonuria (PKU). Using cryo-EM, we determined human BAT1 structures in outward- and inward-open states, revealing an allosteric pocket ~17 Å from the substrate site that is present in the outward-open conformation and has been previously reported. Structure-guided inhibitor design targeting this pocket produced a potent BAT1 inhibitor that locks the transporter in an outward-occluded state and blocks transport. The higher-resolution structures reveal detailed interactions at the binding site, including water-mediated coordination and conformational changes around Leu52. This inhibitor exhibited submicromolar IC against both human and mouse BAT1, and oral administration in PKU model mice increased urinary Phe and reduced plasma Phe levels. These findings provide structural insight into allosteric inhibition of BAT1 and establish a framework for the rational optimization of inhibitors targeting conformationally dynamic allosteric sites in SLC6-family transporters.
External links	Commun Biol / PubMed:42350764
Methods	EM (single particle)
Resolution	2.66 - 3.11 Å
Structure data	62627 9kxt EMDB-62627, PDB-9kxt: Structure of human B0AT1-ACE2 complex with compound1 Method: EM (single particle) / Resolution: 2.7 Å 62628 9kxu EMDB-62628, PDB-9kxu: Structure of human B0AT1-ACE2 complex with compound 2 Method: EM (single particle) / Resolution: 2.87 Å 62629 9kxv EMDB-62629, PDB-9kxv: Structure of human B0AT1-ACE2 complex with compound3 Method: EM (single particle) / Resolution: 2.71 Å 62630 9kxw EMDB-62630, PDB-9kxw: Structure of human B0AT1-ACE2 Method: EM (single particle) / Resolution: 2.66 Å 62631 9kxx EMDB-62631, PDB-9kxx: Inward-open Structure of human B0AT1 Method: EM (single particle) / Resolution: 2.77 Å 62632 9kxy EMDB-62632, PDB-9kxy: Structure of human B0AT1-ACE2 complex with compound1 Method: EM (single particle) / Resolution: 2.82 Å 62633 9kxz EMDB-62633, PDB-9kxz: Structure of human B0AT1-ACE2 complex with compound1 Method: EM (single particle) / Resolution: 2.8 Å 62634 9ky0 EMDB-62634, PDB-9ky0: Structure of human B0AT1-ACE2 complex with compound3 Method: EM (single particle) / Resolution: 2.68 Å 62635 9ky1 EMDB-62635, PDB-9ky1: Structure of human B0AT1-ACE2 complex with compound1 Method: EM (single particle) / Resolution: 2.8 Å 63360 9lsz EMDB-63360, PDB-9lsz: Inward-open Structure of human B0AT1 Method: EM (single particle) / Resolution: 3.11 Å
Chemicals	PDB-1l6u: NMR STRUCTURE OF OXIDIZED ADRENODOXIN ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-HOH: WATER PDB-1l6v: STRUCTURE OF REDUCED BOVINE ADRENODOXIN PDB-1l6w: Fructose-6-phosphate aldolase ChemComp-NA: Unknown entry
Source	homo sapiens (human) mus musculus (house mouse)
Keywords	TRANSPORT PROTEIN / Inhibitor / amino acid transporter / SLC6