6ZGB

glutamate transporter homologue Glttk in complex with a photo cage compound

6ZGB の概要

• エントリーDOI: 10.2210/pdb6zgb/pdb
• 分子名称: Proton/glutamate symporter, SDF family, (2~{S},3~{S})-2-azanyl-3-[(2-nitrophenyl)methoxy]butanedioic acid, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• 機能のキーワード: glutamate transporter, photo cage, membrane protein, transport protein
• 由来する生物種: Thermococcus kodakarensis (strain ATCC BAA-918 / JCM 12380 / KOD1)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 141483.41

構造登録者

Arkhipova, V.,Slotboom, D.J.,Guskov, A. (登録日: 2020-06-18, 公開日: 2021-01-27, 最終更新日: 2024-01-24)

主引用文献

Arkhipova, V.,Fu, H.,Hoorens, M.W.H.,Trinco, G.,Lameijer, L.N.,Marin, E.,Feringa, B.L.,Poelarends, G.J.,Szymanski, W.,Slotboom, D.J.,Guskov, A.
Structural Aspects of Photopharmacology: Insight into the Binding of Photoswitchable and Photocaged Inhibitors to the Glutamate Transporter Homologue.
J.Am.Chem.Soc., 143:1513-1520, 2021

PubMed Abstract: Photopharmacology addresses the challenge of drug selectivity and side effects through creation of photoresponsive molecules activated with light with high spatiotemporal precision. This is achieved through incorporation of molecular photoswitches and photocages into the pharmacophore. However, the structural basis for the light-induced modulation of inhibitory potency in general is still missing, which poses a major design challenge for this emerging field of research. Here we solved crystal structures of the glutamate transporter homologue Glt in complex with photoresponsive transport inhibitors-azobenzene derivative of TBOA (both in and configuration) and with the photocaged compound ONB-hydroxyaspartate. The essential role of glutamate transporters in the functioning of the central nervous system renders them potential therapeutic targets in the treatment of neurodegenerative diseases. The obtained structures provide a clear structural insight into the origins of photocontrol in photopharmacology and lay the foundation for application of photocontrolled ligands to study the transporter dynamics by using time-resolved X-ray crystallography.

PubMed: 33449695
DOI: 10.1021/jacs.0c11336

実験手法

X-RAY DIFFRACTION (3.2 Å)