7SPS

Crystal structure of human glucose transporter GLUT3 bound with exofacial inhibitor SA47

7SPS の概要

• エントリーDOI: 10.2210/pdb7sps/pdb
• 分子名称: Solute carrier family 2, facilitated glucose transporter member 3, methyl N-[(2-{4-[4-(5-fluoro-2-methoxyphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl}phenyl)methyl]-beta-alaninate, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (4 entities in total)
• 機能のキーワード: mfs, hexose transporter, inhibitor, transport protein-inhibitor complex, transport protein/inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 116637.68

構造登録者

Wang, N.,Jiang, X.,Yan, N. (登録日: 2021-11-03, 公開日: 2022-05-18, 最終更新日: 2023-10-18)

主引用文献

Wang, N.,Zhang, S.,Yuan, Y.,Xu, H.,Defossa, E.,Matter, H.,Besenius, M.,Derdau, V.,Dreyer, M.,Halland, N.,He, K.H.,Petry, S.,Podeschwa, M.,Tennagels, N.,Jiang, X.,Yan, N.
Molecular basis for inhibiting human glucose transporters by exofacial inhibitors.
Nat Commun, 13:2632-2632, 2022

PubMed Abstract: Human glucose transporters (GLUTs) are responsible for cellular uptake of hexoses. Elevated expression of GLUTs, particularly GLUT1 and GLUT3, is required to fuel the hyperproliferation of cancer cells, making GLUT inhibitors potential anticancer therapeutics. Meanwhile, GLUT inhibitor-conjugated insulin is being explored to mitigate the hypoglycemia side effect of insulin therapy in type 1 diabetes. Reasoning that exofacial inhibitors of GLUT1/3 may be favored for therapeutic applications, we report here the engineering of a GLUT3 variant, designated GLUT3exo, that can be probed for screening and validating exofacial inhibitors. We identify an exofacial GLUT3 inhibitor SA47 and elucidate its mode of action by a 2.3 Å resolution crystal structure of SA47-bound GLUT3. Our studies serve as a framework for the discovery of GLUTs exofacial inhibitors for therapeutic development.

PubMed: 35552392
DOI: 10.1038/s41467-022-30326-3

実験手法

X-RAY DIFFRACTION (2.3 Å)