Membrane channel forming polypeptides. Molecular conformation and mitochondrial uncoupling activity of antiamoebin, an alpha-aminoisobutyric acid containing peptide.
The conformations of the 16-residue fungal peptide antiamoebin I (Ac-Phe-Aib-Aib-Aib-D-Iva-Gly-Leu-Aib-Aib-Hyp-Gln-D-Iva-Hyp-Aib-Pro-P hol) have been investigated in dimethyl sulfoxide solution by one- and two-dimensional NMR techniques. A substantial number of resonances in the 270-MHz 1H NMR spectrum have been assigned. Intramolecularly hydrogen-bonded (solvent inaccessible) NH groups have been identified by determining solvent and temperature dependence of NH chemical shifts and rates of hydrogen-deuterium exchange. Ten backbone NH groups are inaccessible to solvent, while three NH groups assigned to the Phe(1), Aib(2), and Aib(8) residues are exposed to solvent. Interresidue nuclear Overhauser effects are consistent with psi values of approximately 120 +/- 30 degrees for Phe(1) and Leu(7). The NMR results, together with the stereochemical constraints imposed by the presence of alpha-aminoisobutyryl, isovalyl, prolyl, and 4-hydroxyprolyl residues, favor a highly ordered structure. Two backbone conformations consistent with the data are considered. Antiamoebin is shown to be an effective uncoupler of oxidative phosphorylation in rat liver mitochondria, providing evidence for its membrane-modifying activity.
D000621:Aminoisobutyric Acids; D000818:Animals; D000900:Anti-Bacterial Agents; D007473:Ion Channels / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D010101:Oxygen Consumption / Q000187:drug effects; D054848:Peptaibols; D010455:Peptides; D010456:Peptides, Cyclic / Q000494:pharmacology; D011487:Protein Conformation; D051381:Rats; D013816:Thermodynamics; D014475:Uncoupling Agents
D000621:Aminoisobutyric Acids; D000900:Anti-Bacterial Agents; D007473:Ion Channels; D054848:Peptaibols; D010455:Peptides; D010456:Peptides, Cyclic; D014475:Uncoupling Agents; C006596:antiamoebin; C100049:2-aminoisobutyric acid