L.K. Steinrauf

The molecular structure and some transport properties of valinomycin.

Abstract The antibiotic valinomycin is well known to affect the ion transport behavior of mitochondrial systems. We have determined the molecular structure by X-ray crystallography of this cyclododecadepsipeptide as the potassium aurichloride complex, and find it to be wrapped around the potassium ion coordinated to the oxygen atoms of alternate carbonyl groups, held together by hydrogen bonding, and holding the anion less specifically. We have constructed a diffusion apparatus with which the anion-cation transporting properties of valinomycin can be demonstrated. An equation is given for the equilibrium situation.

Molecular structure of monovalent metal cation complexes of monensin

Abstract The molecular structure of the silver complex of monensin, an antibiotic from Streptomyces cinnamonensis , has been determined by X-ray crystallography. The structure is formed by the monensin wrapping around the silver ion, forming an over-all neutral complex, secured by two hydrogen bonds. The crystal form of the potassium complex is isomorphous with the silver, and the sodium complex, although not isomorphous, is very similar. The nature of the structure of the complex suggests that the biological effects of monensin may well be a consequence of the ability of the antibiotic to make sodium and potassium soluble in lipid portions of cellular structures.

The structure of nigericin

Abstract The molecular structure and the cation binding of nigericin, an antibiotic affecting ion transport and ATPase activity in mitochondria, has been determined by single crystal X-ray crystallography. The molecule is found to be similar to monensin, another antibiotic of similar properties.

Thermodynamic consideration of the ion transporting antibiotics

Abstract A model transport system has been constructed in which nigericin or valinomycin and related antibiotics will catalyze the translocation of ions between aqueous solutions. Equations for the equilibrium distributions of ions have been derived from the Gibbs-Duhem equation, and are in reasonable agreement with the observed distributions. The observed transport behavior is consistent with the molecular structure of the antibiotics from X-ray crystallography.

The binding of barium and calcium ions by the antibiotic beauvericin

Abstract The ion-transporting antibiotic beauvericin has been shown to have a high affinity for calcium and barium ions in addition to the more usual affinity for monovalent cations. As judged by crystallization, extraction into organic solvent, and U-tube transport the cation selectivity is Rb>Ba>K>Na⪢Ca⋙Li. For these studies an improved method for the synthesis of beauvericin has been developed.

Structure of the antibiotic dianemycin.

Abstract X-ray crystallography has been used to determine the structure of dianemycin, C47H78O14, an antibiotic from Streptomyces hydroscopicus , which binds monovalent metal cations. The molecule is a polyether, polyalcohol monocarboxylic acid which completely surrounds the cation forming a complex completed by extensive hydrogen bonding.

The crystal structure of a complex of cycloheptaamylose with 2,5-diiobobenzoic acid

Abstract The molecular structure of the 1:1 complex of cycloheptaamylose with 2,5-diiodobenzoic acid has been determined by X-ray crystallography. The iodine atoms of the guest molecular are disordered and were not used in the structure determination. The cycloheptaamylose molecules form channels in the crystal by means of head to head and tail to tail association using the two-fold crystallographic axis.

Alteration in molecular structure which results in disease: the Met-30 variant of human plasma transthyretin

The structure of a variant transthyretin has been determined by X-ray crystallography at 2.3 A resolution in order to investigate those changes which lead to amyloid formation. This variant transthyretin, in which the internal valyl residue at position 30 is replaced by methionyl, is associated with the most common form of familial amyloidotic polyneuropathy (FAP). Comparison to the known structure of the normal transthyretin tetramer shows that the bulkier methionine residue 30 which lies between the nearly orthogonal beta sheets of the dimer, results in the sheets being displaced an average of 0.4 A. The internal structure of the sheets and of the monomer-monomer interface is maintained. Such global changes may affect the metabolic properties and the tendency towards polymerization of the mutant protein. These findings may form a basis for understanding other amyloid-deposition diseases.

Comparison of the monovalent cation complexes of monensin, nigericin, and dianemycin

Abstract Complexes of monovalent metal cations with the antibiotics monensins, nigericin, and dianemycin have been shown by X-ray crystallography to be functionally very similar. Differences in cation specificities can be attributed to differences in size and flexibility of the antibiotic ligands. Strong similarities between the three antibiotics suggest a common biosynthetic mechanism.

Beauvericin and divalent cations: Crystal structure of the barium complex

Abstract The molecular structure of the 2:2 complex of the cyclohexadepsipeptide antibiotic beauvericin with barium picrate has been determined by X-ray crystallography. The structure serves to confirm previous observations on the bimolecular behavior of beauvericin and of the ions transported by beauvercin. The intimate involvement of the anions in the coordination of the barium also explains observations that the cation specificity of beauvericin in membrane transport depends on the species of anions present.