| Title: | Histidine2 of the alpha-factor of Saccharomyces cerevisiae is not essential for binding to its receptor or for biological activity |
| Author(s): | Levin Y; Khare RK; Abel G; Hill D; Eriotou-Bargiota E; Becker JM; Naider F; |
| Address: | "Department of Chemistry, College of Staten Island, City University of New York 10301" |
| ISSN/ISBN: | 0006-2960 (Print) 0006-2960 (Linking) |
| Abstract: | "Seven His2 analogs of the Saccharomyces cerevisiae [Nle12]alpha-factor, WXWLQLKPGQP(Nle)Y, where X = beta-D-thienylalanine, beta-L-thienylalanine, 1-D-methylhistidine, 1-L-methylhistidine, 3-D-methylhistidine, 3-L-methylhistidine, and beta-3-L-pyridylalanine, were synthesized and purified to homogeneity. Assays were carried out on binding to the alpha-factor receptor and of biological activity determined by either growth arrest or morphological changes in target cells. In the L-isomer, replacement of the imidazole of histidine by thiophene or 3-pyridyl groups or derivatization of either nitrogen of the imidazole ring by methylation resulted in a 2-100-fold decrease in bioactivity. D-Isomers of the beta-thienylalanyl-, 1-methylhistidinyl-, or 3-methylhistidinyl-alpha-factors did not possess measurable bioactivity with the exception of comparatively low activity of the 3-D-methylhistidinyl and 1-D-methylhistidinyl-alpha-factors in the morphogenesis assay. In contrast, both active and inactive analogs demonstrated binding affinities 10-20-fold less than that of [Nle12]alpha-factor. These results indicate that the histidine residue of alpha-factor is not required for binding to the receptor or for biological activity and that bioactivity and binding can be dissociated through the use of pheromone analogs" |
| Keywords: | "Amino Acid Sequence Binding, Competitive Chromatography, High Pressure Liquid Histidine/analogs & derivatives/*chemistry Magnetic Resonance Spectroscopy Mating Factor Methylhistidines/chemistry Molecular Sequence Data Peptides/*chemistry/metabolism/pharma;" |
| Notes: | "MedlineLevin, Y Khare, R K Abel, G Hill, D Eriotou-Bargiota, E Becker, J M Naider, F eng GM22086/GM/NIGMS NIH HHS/ GM22087/GM/NIGMS NIH HHS/ Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. 1993/08/17 Biochemistry. 1993 Aug 17; 32(32):8199-206. doi: 10.1021/bi00083a021" |
