Gramicidin is a heterogeneous mixture of six antibiotic compounds divided into three catagories: Gramicidin A, B and C, all of which are obtained from the soil bacterial species Bacillus brevis and called collectily Gramicidin D. Gramicidin D are linear pentadecapeptides, that is, they are long protein chains made up of 15 amino acids. This is in contrast to Gramicidin S which is a cyclic peptide chain. more...
Gramicidin is especially effective against gram-positive bacteria but induces hemolysis in lower concentrations than bacteria cell death thus cannot be administered internally. It is used primarily as a topical antibiotic and is one of the three constituents of consumer antibiotic Neosporin Ophthalmic Solution. In 1939 the American microbiologist René Dubos isolated the substance tyrothricin and later showed that it was composed of two substances, gramicidin (20%) and tyrocidine (80%). These were the first antibiotics to be manufactured commercially.
Gramicidin is composed of the general foruma: formyl-L-X-Gly-L-Ala-D-Leu-L-Ala-D-Val-L-Val-DVal-L-Trp-D-Leu-L-Y-D-Leu-L-Trp-D-Leu-L-Trp-ethanolamine
X and Y depend upon the gramicidin molecule. There exists valine and isoleucine variants of all three gramicidin species and 'X' can be either. Y determines which is which; in the place of Y Gramicidin A contains Tryptophan, B contains Phenylalanine and C contains Tyrosine. Also note the alternating stereochemical configurations (in the form of D and L) of the amino acids: this is vital to the formation of the ß-helix.
Gramicidin's bactericidal activity is a result of increasing the permeability of the bacterial cell wall allowing inorganic cations to travel through unrestricted, thereby destroying the ion gradient between the cytoplasm and the extracellular environment.
In gramicidin D, two strands are held end to end by hydrogen bonding within the cell bilayer. The alternating stereochemistry allows the amino acid functionalities to point outward creating a central pore which freely allows cations to pass. Thus gramicidin A is basically functions as a channel. The bound helix can insert itself into the lipid bilayer of a cell and destroy the ion gradient thereby killing the cell.
That gramicidin D functions as a channel was demonstrated by Hladky and Haydon, who investigated the unit conductance channel. In general, gramicidin channels are ideally selective for monovalent cations and the single-channel conductances for the alkali cations are ranked in the same order as the aqueous mobilities of these ions. Divalent cations like Ca-2+ block the channel by binding near the mouth of the channel. So it is basically impermeable to divalent cations. It also excludes anions. Cl- in particular is excluded from the channel because its hydration shell is thermodynamically stronger than that of most monovalent cations. The channel is permeable to most monovalent cations, which move through the channel in single file. The channel is filled with about six water molecules, almost all of which must be displaced when an ion is transported. Thus, ions moving through the gramicidin pore carry along a single file of water molecules. Such a flux of ion and water molecules is known as flux coupling. In the presence of a second type of permeable ion, the two ions couple their flux as well. Like Valinomycin and Nonactin, the gramicidin channel is selective for potassium over sodium but only slightly so. It has a permeability ration of 2.9. It is impermeable to anions but there are conditions under which some anion permeation may be observed. Its ability to bind and transport cations is due to the presence of cation-binding sites in the channel. Specifically, there are two such binding sites, one strong and the other weak.
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