Gramicidin

Gramicidin
Systematic (IUPAC) name
Bacillus brevis gramicidin D
Identifiers
CAS number	1405-97-6
ATC code	R02AB30
PubChem	?
DrugBank	BTD00036
Chemical data
Formula	C99H140N20O17
Mol. mass	1882.3 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?

WikiDoc Resources for Gramicidin
Articles
Most recent articles on Gramicidin Most cited articles on Gramicidin Review articles on Gramicidin Articles on Gramicidin in N Eng J Med, Lancet, BMJ
Media
Powerpoint slides on Gramicidin Images of Gramicidin Photos of Gramicidin Podcasts & MP3s on Gramicidin Videos on Gramicidin
Evidence Based Medicine
Cochrane Collaboration on Gramicidin Bandolier on Gramicidin TRIP on Gramicidin
Clinical Trials
Ongoing Trials on Gramicidin at Clinical Trials.gov Trial results on Gramicidin Clinical Trials on Gramicidin at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Gramicidin NICE Guidance on Gramicidin NHS PRODIGY Guidance FDA on Gramicidin CDC on Gramicidin
Books
Books on Gramicidin
News
Gramicidin in the news Be alerted to news on Gramicidin News trends on Gramicidin
Commentary
Blogs on Gramicidin
Definitions
Definitions of Gramicidin
Patient Resources / Community
Patient resources on Gramicidin Discussion groups on Gramicidin Patient Handouts on Gramicidin Directions to Hospitals Treating Gramicidin Risk calculators and risk factors for Gramicidin
Healthcare Provider Resources
Symptoms of Gramicidin Causes & Risk Factors for Gramicidin Diagnostic studies for Gramicidin Treatment of Gramicidin
Continuing Medical Education (CME)
CME Programs on Gramicidin
International
Gramicidin en Espanol Gramicidin en Francais
Business
Gramicidin in the Marketplace Patents on Gramicidin
Experimental / Informatics
List of terms related to Gramicidin

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Gramicidin is a heterogeneous mixture of six antibiotic compounds, Gramicidins A, B and C, making up 80%, 6%, and 14% respectively, all of which are obtained from the soil bacterial species Bacillus brevis and called collectively Gramicidin D. Gramicidin D are linear pentadecapeptides; that is chains made up of 15 amino acids. This is in contrast to Gramicidin S which is a cyclic peptide chain. Gramicidin is active against Gram-positive bacteria, except for the Gram-positive bacilli, and against select Gram-negative organisms, such as Neisseria bacteria. Its therapeutic use is limited to topical application as it induces hemolysis in lower concentrations than bacteria cell death thus cannot be administered internally. The exterior epidermis is composed of dead cells, thus applying it to the surface of the skin will not cause harm. It is used primarily as a topical antibiotic and is one of the three constituents of consumer antibiotic Neosporin Ophthalmic Solution. In 1939 the French-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.

Composition and Structure

Gramicidin is composed of the general formula: formyl-L-X-Gly-L-Ala-D-Leu-L-Ala-D-Val-L-Val-D-Val-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 β-helix.

The chain assembles inside of the hydrophobic interior of the cellular lipid bilayer to form a β-helix. The helix itself is not long enough to span the membrane but it dimerizes to form the elongated channel needed to span the whole membrane.

The structure of gramicidin head-to-head dimer in micelles and lipid bilayers was determined by solution and solid state NMR. In organic solvents and crystals, this peptide forms different types of non-native double helices.

Pharmacological Effect

Gramicidin's bactericidal activity is a result of increasing the permeability of the bacterial cell wall allowing inorganic monovalent cations (e.g. H⁺) to travel through unrestricted, thereby destroying the ion gradient between the cytoplasm and the extracellular environment.

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.

References

• Ketchem RR, Lee KC, Huo S, Cross TA (1996). "Macromolecular structural elucidation with solid-state NMR-derived orientational constraints". J. Biomol. NMR 8 (1): 1–14. doi:10.1007/BF00198135. PMID 8810522.

• Townsley LE, Tucker WA, Sham S, Hinton JF (2001). "Structures of gramicidins A, B, and C incorporated into sodium dodecyl sulfate micelles". Biochemistry 40 (39): 11676–86. doi:10.1021/bi010942w. PMID 11570868.

External links

• UMich Orientation of Proteins in Membranes protein/pdbid-1grm - Gramicidin A channel

de:Gramicidin it:Gramicidina