TCDB is operated by the Saier Lab Bioinformatics Group

1.D.1 The Gramicidin A (Gramicidin A) Channel Family

Gramicidin A, a pentadecapeptide antibiotic, is made by Bacillus brevis and forms channels in synthetic and natural bilayers that are selective for monovalent cations such as H , Tl , NH4+ and the alkali metals. X-ray crystal structures, 15N-NMR and CD data reveal alternate structures that Gramicidin can assume. The functional channel in lipid bilayers is probably a transmembrane helical dimer. Two monomeric β-helices meet at their N-termini in the center of the membrane. Transport of ions may occur by single file transfer through the gramicidin channel. Gramicidin also forms double helical structures which consists of two hydrogen bonded β-strands that are rolled up to form double β-helicies which can span the thickness of the bilayer. Only under limited conditions do double helical forms conduct ions.  Some aspects of its structure and mechanism are debatable (Andersen et al. 2005; Kelkar and Chattopadhyay 2007), and one report suggests that gramicidin may not form pores (Ashrafuzzaman et al. 2008).  Gramicidin A can catalyzed phospholipid flipping from one monolayer to the other (Anglin et al. 2007). Gramicidin can passively translocate across membranes (McKay et al. 2018).

Gramicidin is not synthesized by a ribosomal-dependent mechanism, and it contains six D amino acids, all leucine and valine residues. The sequence of gramicidin A is: HCO-L-Val1-Gly2-L-Ala3-D-Leu4-L-Ala5-D-Val6-L-Val7-D-Val8-L-Trp9-D-Leu10-L-Trp11-D-Leu12-L-Trp13-D-Leu14-L-Trp15-NHCH2-CH2OH. Because it is not encoded by a gene, gramicidin is not included in the databases, and no accession number is available. In contrast to valinomycin which complexes with K and shuttles across the membrane, in a ''carrier''-like process, gramicidin forms a static channel and serves as the prototype for protein-mediated channel formation across biological membranes.  Gramicidin has been shown to block tumor growth and angiogenesis (David et al. 2014).  Applications of pore-forming gramicidin include small- and macromolecule-sensing, targeted cancer therapy and drug delivery (Gurnev and Nestorovich 2014).

In addition to its role as a K+ channel, Gramicidin increases lipid flip-flop (lipid scrambling between the two monolayers of the bilayer) in both symmetric and asymmetric lipid vesicles (Doktorova et al. 2019).

The generalized reaction catalyzed by gramicidin is:

Monovalent cation (in)  Monovalent cation (out).

References associated with 1.D.1 family:

Andersen, O.S., R.E. Koeppe, 2nd, and B. Roux. (2005). Gramicidin channels. IEEE Trans Nanobioscience 4: 10-20. 15816168
Anglin, T.C., J. Liu, and J.C. Conboy. (2007). Facile lipid flip-flop in a phospholipid bilayer induced by gramicidin A measured by sum-frequency vibrational spectroscopy. Biophys. J. 92: L1-13. 17071658
Ashrafuzzaman, M., O.S. Andersen, and R.N. McElhaney. (2008). The antimicrobial peptide gramicidin S permeabilizes phospholipid bilayer membranes without forming discrete ion channels. Biochim. Biophys. Acta. 1778: 2814-2822. 18809374
Burkhart, B.M., N. Li, D.A. Langs, W.A. Pangborn and W.L. Duax (1998). The conducting form of gramicidin A is a right-handed double-stranded double helix. Proc. Natl. Acad. Sci. USA 95: 12950—12955. 9789021
David JM., Owens TA., Inge LJ., Bremner RM. and Rajasekaran AK. (2014). Gramicidin A blocks tumor growth and angiogenesis through inhibition of hypoxia-inducible factor in renal cell carcinoma. Mol Cancer Ther. 13(4):788-99. 24493697
Doktorova, M., F.A. Heberle, D. Marquardt, R. Rusinova, R.L. Sanford, T.A. Peyear, J. Katsaras, G.W. Feigenson, H. Weinstein, and O.S. Andersen. (2019). Gramicidin Increases Lipid Flip-Flop in Symmetric and Asymmetric Lipid Vesicles. Biophys. J. [Epub: Ahead of Print] 30755300
Gurnev, P.A. and E.M. Nestorovich. (2014). Channel-forming bacterial toxins in biosensing and macromolecule delivery. Toxins (Basel) 6: 2483-2540. 25153255
Kelkar, D.A. and A. Chattopadhyay. (2007). The gramicidin ion channel: a model membrane protein. Biochim. Biophys. Acta. 1768: 2011-2025. 17572379
McKay, M.J., F. Afrose, R.E. Koeppe, 2nd, and D.V. Greathouse. (2018). Helix formation and stability in membranes. Biochim. Biophys. Acta. Biomembr 1860: 2108-2117. 29447916
Wallace, B.A. (2000). Common structural features in gramicidin and other ion channels. Bioessays 22: 227-234. 10684582