Amide molecular clocks in drosophila proteins: potential regulators of aging and other processes

After synthesis and folding, peptides and proteins undergo changes in charge and conformation through nonenzymatic deamidation of asparaginyl and glutaminyl residues. Each amide has a specific deamidation rate that is genetically determined by the sequence of residues immediately adjacent in the peptide chain and by secondary, tertiary, and quaternary structure. By means of experimentally verified computations, we have determined the deamidation rates of 49 Drosophila peptides and proteins. These rates demonstrate that deamidation provides molecular clocks that are suitable for the regulation of Drosophila aging, development, and other biochemical processes. We have also determined the rates of deamidation for 17,886 other proteins from a wide variety of organisms. The distribution function of these deamidation rates demonstrates the suitability of amide residues as biomolecular clocks. (C) 2004 Elsevier Ireland Ltd. All rights reserved.