title: Stabilizing effect of D-alanine2 in gramicidin channels.
abstract: We have investigated the effects of replacing Gly2 by D-Ala2 in gramicidin A (gA) analogues that have either L-Val, L-Ala, or Gly as the formyl-N-terminal residue. Circular dichroism, two-dimensional nuclear magnetic resonance, and hybrid channel experiments all show that [Ala1,D-Ala2]gA channels are structurally equivalent to the native [Val1,Gly2]gA channels, being formyl-NH-to-formyl-NH dimers of single-stranded, right-handed beta 6.3 helices. Replacing the Val1 of gA by Ala or Gly decreases the average channel duration. Replacing Gly2 by D-Ala in [Val1,Gly2]gA increases the average channel duration 4-fold and the single-channel conductance by approximately 15%; replacing Gly2 with D-Ala in [Ala1,Gly2]gA or [Gly1,Gly2]-gA leads in each case to a 10-fold increase in the average channel duration with only modest changes in the single-channel conductance, which depends on the identity of the position-one residue and the permeant ion. These results illustrate the importance of neighboring-residue side chain and backbone interactions for the modulation of channel properties.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville 72701, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Mattice
authors.forename: R E
authors.initials: RE
authors.lastname: Koeppe
authors.forename: L L
authors.initials: LL
authors.lastname: Providence
authors.forename: O S
authors.initials: OS
authors.lastname: Andersen
mesh_terms: D000409:Alanine / Q000737:chemistry*; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D004355:Drug Stability; D004553:Electric Conductivity; D005998:Glycine / Q000737:chemistry; D006096:Gramicidin / Q000737:chemistry* / Q000378:metabolism; D007473:Ion Channels / Q000737:chemistry* / Q000502:physiology; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: D007473:Ion Channels; D046911:Macromolecular Substances; D006096:Gramicidin; D000409:Alanine; D005998:Glycine