4POP

ThiT with LMG139 bound

4POP の概要

• エントリーDOI: 10.2210/pdb4pop/pdb
• 関連するPDBエントリー: 3RLB 4POV
• 分子名称: Thiamine transporter ThiT, 3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL, 4-[(4-amino-2-methylpyrimidin-5-yl)methyl]-3-methylthiophene-2-carbaldehyde, ... (11 entities in total)
• 機能のキーワード: s-component, thiamine-binding protein, ecf module, membrane, protein binding
• 由来する生物種: Lactococcus lactis subsp. cremoris
• 細胞内の位置: Cell membrane ; Multi-pass membrane protein : A2RI47
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 50300.28

構造登録者

Swier, L.J.Y.M.,Guskov, A.,Slotboom, D.J. (登録日: 2014-02-26, 公開日: 2014-09-17, 最終更新日: 2024-02-28)

主引用文献

Swier, L.J.,Monjas, L.,Guskov, A.,de Voogd, A.R.,Erkens, G.B.,Slotboom, D.J.,Hirsch, A.K.
Structure-Based Design of Potent Small-Molecule Binders to the S-Component of the ECF Transporter for Thiamine.
Chembiochem, 16:819-826, 2015

PubMed Abstract: Energy-coupling factor (ECF) transporters are membrane-protein complexes that mediate vitamin uptake in prokaryotes. They bind the substrate through the action of a specific integral membrane subunit (S-component) and power transport by hydrolysis of ATP in the three-subunit ECF module. Here, we have studied the binding of thiamine derivatives to ThiT, a thiamine-specific S-component. We designed and synthesized derivatives of thiamine that bind to ThiT with high affinity; this allowed us to evaluate the contribution of the functional groups to the binding affinity. We determined six crystal structures of ThiT in complex with our derivatives. The structure of the substrate-binding site in ThiT remains almost unchanged despite substantial differences in affinity. This work indicates that the structural organization of the binding site is robust and suggests that substrate release, which is required for transport, requires additional changes in conformation in ThiT that might be imposed by the ECF module.

PubMed: 25676607
DOI: 10.1002/cbic.201402673

実験手法

X-RAY DIFFRACTION (2.2 Å)