A novel conformation of valinomycin in its barium complex

Abstract

Knowledge of the molecular mechanisms involved in ionophore-mediated cation transport would be valuable for understanding many essential functions of biological membranes. Cations are transported in several stages, such as formation of the ionophore-cation complex, diffusion across the cell membrane and subsequent release of the cation. Several conformational rearrangements are involved in this process, and so a detailed understanding of all the conformational possibilities of the ionophore seems to be essential for elucidating the molecular mechanism of ion transport. We are carrying out spectroscopic and crystallographic studies to explore the possible conformational stages of ionophores by complexing them, in different solvents, with cations of various sizes and charges. We report here a novel conformation of the ionophore valinomycin in its barium complex. It can be described as an extended depsipeptide chain, without interval hydrogen bonds, wound in the form of an ellipse with the two barium ions located at the foci.

The crystal structure of a valinomycin•2Ca2+ complex and the multi-step solution equilibria in acetonitrile characterised by 1H NMR, UV–Vis, and mass spectrometry

“…The valinomycin complex with two equivalents of barium ions, [VBa 2 (ClO 4 ) 2 (H 2 O) 3 ](ClO 4 ) 2 , is the only other divalent cation complex for which an X-ray crystal structure has been reported (21). Despite the significant difference in the ionic radii (100 pm for Ca 2+ and 135 pm for Ba 2+ ) (25), the barium and calcium complexes share many common features.…”

“…The Ca 2+ centres are six-coordinate and octahedral, while the Ba 2+ centres are 7-and 9-coordinate (21). The two Ca 2+ centres are bridged by two triflates in a κ-mode, whereas the two Ba centres are bridged by two perchlorates in a μ-mode through just one O atom.…”

“…Interactions of Group 2 divalent metal ions, including calcium, with valinomycin in non-physiological solutions have been previously investigated in the 1980s by Easwaran and co-workers (21). These studies, based on the CD and NMR spectroscopic analyses in acetonitrile, concluded that the larger Sr 2+ and Ba 2+ ions were found to form V 2 M, VM and VM 2 complexes (V = valinomycin, M = cation), while the smaller Mg 2+ and Ca 2+ formed only V 2 M and VM complexes.…”

“…These studies, based on the CD and NMR spectroscopic analyses in acetonitrile, concluded that the larger Sr 2+ and Ba 2+ ions were found to form V 2 M, VM and VM 2 complexes (V = valinomycin, M = cation), while the smaller Mg 2+ and Ca 2+ formed only V 2 M and VM complexes. The most detailed study was with Ba 2+ ion, including an X-ray crystal structure (21). The binding constants for V 2 M and VM were reported for Mg 2+ and Ca 2+ based on CD titrations (21), but not for Sr 2+ and Ba 2+ due to the 'complicated spectroscopic behaviour' .…”

Visualizing Cyclic Peptide Hydration at the Single-Molecule Level

“…Valinomycin is a cyclic peptide and an important ion carrier for the specific transport of potassium ions (K + ions) responsible for maintaining K + ions balance between the two sides of the cell membrane5. Many studies, including theoretical simulations and experimental measurements, have been performed to elucidate the conformations, ion-transport dynamics and ion-transport mechanism of valinomycin67891011. The conformations under various environments have been widely studied because ion transport is always accompanied by a conformational transition6.…”