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Publication Abstract from PubMed

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.

Structure-Based Design of Potent Small-Molecule Binders to the S-Component of the ECF Transporter for Thiamine.,Swier LJ, Monjas L, Guskov A, de Voogd AR, Erkens GB, Slotboom DJ, Hirsch AK Chembiochem. 2015 Mar 23;16(5):819-26. doi: 10.1002/cbic.201402673. Epub 2015 Feb, 12. PMID:25676607^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.