Valinomycin
Encyclopedia
Valinomycin is a dodecadepsipeptide
antibiotic
.
Valinomycin is obtained from the cells of several Streptomyces
strains, among which "S. tsusimaensis" and S. fulvissimus.
It is a member of the group of natural neutral ionophore
s because it does not have a residual charge. It consists of enantiomer
s D- and L-valine (Val), D-hydroxyvaleric acid and L-lactic acid
. Structures are alternately bound via amide
and ester
bridges. Valinomycin is highly selective for potassium
ions over sodium
ions within the cell membrane
. It functions as a potassium-specific transporter and facilitates the movement of potassium ions through lipid membranes "down" an electrochemical potential gradient. The stability constant
K for the potassium-valinomycin complex is 106 and for the sodium-valinomycin complex only 10.
This difference is important for maintaining the selectivity of valinomycin for the transport of potassium ions (and not sodium ions) in biological systems.
s and ester
s to form a macrocyclic molecule. The twelve carbonyl
groups are essential for the binding of metal ions, and also for solvation
in polar solvent
. The isopropyl
and methyl groups are responsible for solvation in nonpolar solvent
s.
Along with its shape and size this molecular duality is the main reason for its binding properties. K+ ions are octahedrally coordinated in a square bipyramidal geometry by 6 carbonyl bonds from Val. In this space of 1.33 Angstrom, Na+ with its 1.57 Angstrom radius, does not fit, leading to a 10,000x selectivity for K+ ions over Na+. For polar solvents, valinomycin will mainly expose the carbonyls to the solvent and in nonpolar solvents the isopropyl groups are located predominantly on the exterior of the molecule. This conformation changes when valinomycin is bound to a potassium ion. The molecule is "locked" into a conformation with the isopropyl groups on the exterior. It is not actually locked into configuration because the size of the molecule makes it highly flexible, but the potassium ion gives some degree of coordination to the macromolecule.
Valinomycin acts as a nonmetallic isoforming agent in potassium selective electrode
s.
Depsipeptide
A depsipeptide is a peptide in which one or more of the amide bonds are replaced by ester bonds.Depsipeptides have often been used in research to probe the importance of hydrogen bond networks in protein folding kinetics and thermodynamics. They are also found in nature as natural products...
antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
.
Valinomycin is obtained from the cells of several Streptomyces
Streptomyces
Streptomyces is the largest genus of Actinobacteria and the type genus of the family Streptomycetaceae. Over 500 species of Streptomyces bacteria have been described. As with the other Actinobacteria, streptomycetes are gram-positive, and have genomes with high guanine and cytosine content...
strains, among which "S. tsusimaensis" and S. fulvissimus.
It is a member of the group of natural neutral ionophore
Ionophore
An ionophore is a lipid-soluble molecule usually synthesized by microorganisms to transport ions across the lipid bilayer of the cell membrane...
s because it does not have a residual charge. It consists of enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
s D- and L-valine (Val), D-hydroxyvaleric acid and L-lactic acid
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...
. Structures are alternately bound via amide
Amide
In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
and ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
bridges. Valinomycin is highly selective for potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
ions over sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
ions within the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
. It functions as a potassium-specific transporter and facilitates the movement of potassium ions through lipid membranes "down" an electrochemical potential gradient. The stability constant
Stability constant
Stability constant may refer to:*Equilibrium constant*Acid dissociation constant*Stability constants of complexes...
K for the potassium-valinomycin complex is 106 and for the sodium-valinomycin complex only 10.
This difference is important for maintaining the selectivity of valinomycin for the transport of potassium ions (and not sodium ions) in biological systems.
Structure
Valinomycin is a dodecadepsipeptide, that is, it is made of twelve alternating amino acidAmino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s and ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
s to form a macrocyclic molecule. The twelve carbonyl
Carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups....
groups are essential for the binding of metal ions, and also for solvation
Solvation
Solvation, also sometimes called dissolution, is the process of attraction and association of molecules of a solvent with molecules or ions of a solute...
in polar solvent
Solvent
A solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution that is soluble in a certain volume of solvent at a specified temperature...
. The isopropyl
Isopropyl
In organic chemistry, isopropyl is a propyl with a group attached to the secondary carbon. If viewed as a functional group an isopropyl is an organic compound with a propyl group attached at its secondary carbon.The bond is therefore on the middle carbon....
and methyl groups are responsible for solvation in nonpolar solvent
Solvent
A solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution that is soluble in a certain volume of solvent at a specified temperature...
s.
Along with its shape and size this molecular duality is the main reason for its binding properties. K+ ions are octahedrally coordinated in a square bipyramidal geometry by 6 carbonyl bonds from Val. In this space of 1.33 Angstrom, Na+ with its 1.57 Angstrom radius, does not fit, leading to a 10,000x selectivity for K+ ions over Na+. For polar solvents, valinomycin will mainly expose the carbonyls to the solvent and in nonpolar solvents the isopropyl groups are located predominantly on the exterior of the molecule. This conformation changes when valinomycin is bound to a potassium ion. The molecule is "locked" into a conformation with the isopropyl groups on the exterior. It is not actually locked into configuration because the size of the molecule makes it highly flexible, but the potassium ion gives some degree of coordination to the macromolecule.
Applications
Valinomycin was recently reported to be the most potent agent against severe acute respiratory-syndrome coronavirus (SARS-CoV) in infected Vero E6 cells.Valinomycin acts as a nonmetallic isoforming agent in potassium selective electrode
Potassium selective electrode
Potassium selective electrodes are a type of ion selective electrode used in biochemical and biophysical research, where measurements of potassium concentration in an aqueous solution are required, usually on a real time basis....
s.
External links
- Chemical Safety Regulations from New Jersey Department of Health.
- Health information on Scorecard.
- Valinomycin from FermentekFermentekFermentek Ltd. is a biotechnological company, located in Atarot industrial zone, Jerusalem, Israel, specializing in the research, development and manufacture of biologically active, natural products isolated from microorganisms as well as from other natural sources such as plants and algae.The main...
.