6ZL4

the structure of glutamate transporter homologue GltTk in complex with the photo switchable compound (cis)

Summary for 6ZL4

• Entry DOI: 10.2210/pdb6zl4/pdb
• Descriptor: Proton/glutamate symporter, SDF family, (2~{S},3~{S})-2-azanyl-3-[[4-[2-(4-methoxyphenyl)hydrazinyl]phenyl]methoxy]butanedioic acid, DECYL-BETA-D-MALTOPYRANOSIDE, ... (8 entities in total)
• Functional Keywords: glutamate transporter, amino acid transporter, photoisomerization, membrane protein, transport protein
• Biological source: Thermococcus kodakarensis
• Total number of polymer chains: 3
• Total formula weight: 146044.49

Authors

Arkhipova, V.,Slotboom, D.J.,Guskov, A. (deposition date: 2020-06-30, release date: 2021-01-27, Last modification date: 2024-01-31)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3 Å)