EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Transport and inhibition mechanism of the human SGLT2-MAP17 glucose transporter.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 31, Issue 1, Page 159-169, Year 2024
掲載日	2023年12月6日
著者	Masahiro Hiraizumi / Tomoya Akashi / Kouta Murasaki / Hiroyuki Kishida / Taichi Kumanomidou / Nao Torimoto / Osamu Nureki / Ikuko Miyaguchi /
PubMed 要旨	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.
リンク	Nat Struct Mol Biol / PubMed:38057552 / PubMed Central
手法	EM (単粒子)
解像度	2.8 - 3.3 Å
構造データ	34610 8hb0 EMDB-34610, PDB-8hb0: Structure of human SGLT2-MAP17 complex with TA1887 手法: EM (単粒子) / 解像度: 2.9 Å 34673 8hdh EMDB-34673, PDB-8hdh: Structure of human SGLT2-MAP17 complex with Canagliflozin 手法: EM (単粒子) / 解像度: 3.1 Å 34705 8hez EMDB-34705, PDB-8hez: Structure of human SGLT2-MAP17 complex with Dapagliflozin 手法: EM (単粒子) / 解像度: 2.8 Å 34737 8hg7 EMDB-34737, PDB-8hg7: Structure of human SGLT2-MAP17 complex with Sotagliflozin 手法: EM (単粒子) / 解像度: 3.1 Å 34823 8hin EMDB-34823, PDB-8hin: Structure of human SGLT2-MAP17 complex with Phlorizin 手法: EM (単粒子) / 解像度: 3.3 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-KZ3: (2R,3R,4S,5S,6R)-2-[3-[(4-cyclopropylphenyl)methyl]-4-fluoranyl-indol-1-yl]-6-(hydroxymethyl)oxane-3,4,5-triol / TA-1887 ChemComp-NA: Unknown entry / ナトリウムカチオン ChemComp-HOH: 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 / カナグリフロジン ChemComp-LE6: (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol / 1-[3-(β-D-グルコピラノシル)-6-クロロベンジル]-4-エトキシベンゼン 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 / フロリジン
由来	homo sapiens (ヒト)
キーワード	TRANSPORT PROTEIN / Ion transport / Sodium transport / Sugar transport / Symport / Transport