title: Engineering the gramicidin channel.
abstract: The chemical design or redesign of proteins with significant biological activity presents formidable challenges. Ion channels offer advantages for such design studies because one can examine the function of single molecular entities in real time. Gramicidin channels are attractive for study because of their known structure and exceptionally well-defined function. This article focuses on amino acid sequence changes that redesign the structure or function of gramicidin channels. New, and functional, folded states have been achieved. In some cases, a single amino acid sequence can give rise to several (up to three) functional conformations. Single amino acid substitutions confer voltage-dependent channel gating. The findings provide insight into the folding of integral membrane proteins, the importance of tryptophan residues at the membrane/water interface, and the mechanism of channel gating.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville 72701, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Koeppe
authors.forename: O S
authors.initials: OS
authors.lastname: Anderson
mesh_terms: D000595:Amino Acid Sequence; D015195:Drug Design; D006096:Gramicidin / Q000737:chemistry* / Q000378:metabolism; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism; D008051:Lipid Bilayers; D008969:Molecular Sequence Data; D011487:Protein Conformation; D015202:Protein Engineering; D017510:Protein Folding; D014867:Water / Q000378:metabolism
chemical_list: D007473:Ion Channels; D008051:Lipid Bilayers; D014867:Water; D006096:Gramicidin