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	Transport and inhibition mechanism of the human SGLT2-MAP17 glucose transporter.
Journal, issue, pages	Nat Struct Mol Biol, Vol. 31, Issue 1, Page 159-169, Year 2024
Publish date	Dec 6, 2023
Authors	Masahiro Hiraizumi / Tomoya Akashi / Kouta Murasaki / Hiroyuki Kishida / Taichi Kumanomidou / Nao Torimoto / Osamu Nureki / Ikuko Miyaguchi /
PubMed Abstract	Sodium-glucose cotransporter 2 (SGLT2) is imporant in glucose reabsorption. SGLT2 inhibitors suppress renal glucose reabsorption, therefore reducing blood glucose levels in patients with type 2 ...Sodium-glucose cotransporter 2 (SGLT2) is imporant in glucose reabsorption. SGLT2 inhibitors suppress renal glucose reabsorption, therefore reducing blood glucose levels in patients with type 2 diabetes. We and others have developed several SGLT2 inhibitors starting from phlorizin, a natural product. Using cryo-electron microscopy, we present the structures of human (h)SGLT2-MAP17 complexed with five natural or synthetic inhibitors. The four synthetic inhibitors (including canagliflozin) bind the transporter in the outward conformations, while phlorizin binds it in the inward conformation. The phlorizin-hSGLT2 interaction exhibits biphasic kinetics, suggesting that phlorizin alternately binds to the extracellular and intracellular sides. The Na-bound outward-facing and unbound inward-open structures of hSGLT2-MAP17 suggest that the MAP17-associated bundle domain functions as a scaffold, with the hash domain rotating around the Na-binding site. Thus, Na binding stabilizes the outward-facing conformation, and its release promotes state transition to inward-open conformation, exhibiting a role of Na in symport mechanism. These results provide structural evidence for the Na-coupled alternating-access mechanism proposed for the transporter family.
External links	Nat Struct Mol Biol / PubMed:38057552 / PubMed Central
Methods	EM (single particle)
Resolution	2.8 - 3.3 Å
Structure data	34610 8hb0 EMDB-34610, PDB-8hb0: Structure of human SGLT2-MAP17 complex with TA1887 Method: EM (single particle) / Resolution: 2.9 Å 34673 8hdh EMDB-34673, PDB-8hdh: Structure of human SGLT2-MAP17 complex with Canagliflozin Method: EM (single particle) / Resolution: 3.1 Å 34705 8hez EMDB-34705, PDB-8hez: Structure of human SGLT2-MAP17 complex with Dapagliflozin Method: EM (single particle) / Resolution: 2.8 Å 34737 8hg7 EMDB-34737, PDB-8hg7: Structure of human SGLT2-MAP17 complex with Sotagliflozin Method: EM (single particle) / Resolution: 3.1 Å 34823 8hin EMDB-34823, PDB-8hin: Structure of human SGLT2-MAP17 complex with Phlorizin Method: EM (single particle) / Resolution: 3.3 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine ChemComp-KZ3: (2R,3R,4S,5S,6R)-2-[3-[(4-cyclopropylphenyl)methyl]-4-fluoranyl-indol-1-yl]-6-(hydroxymethyl)oxane-3,4,5-triol ChemComp-NA: Unknown entry ChemComp-HOH: WATER / Water ChemComp-L3R: (2~{S},3~{R},4~{R},5~{S},6~{R})-2-[3-[[5-(4-fluorophenyl)thiophen-2-yl]methyl]-4-methyl-phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol ChemComp-LE6: (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol ChemComp-LFL: (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyl-oxane-3,4,5-triol ChemComp-LN9: 1-[2-[(2S,3R,4S,5S,6R)-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-4,6-bis(oxidanyl)phenyl]-3-(4-hydroxyphenyl)propan-1-one
Source	homo sapiens (human)
Keywords	TRANSPORT PROTEIN / Ion transport / Sodium transport / Sugar transport / Symport / Transport