K: Coordinated amino acid changes in homologous protein families. Protein Eng

In the tobamovirus coat protein family, amino acid residues at some spatially close positions are found to be substituted in a coordinated manner [ Altschuh et al. (1987) J. Mol. Biol., 193,693]. Therefore, these positions snow an identical pattern of amino acid substitutions when amino add sequences of these homologous proteins are aligned. Based on this principle, coordinated substitutions have been searched for in three additional protein families: serine proteases, cysteine proteases and the haemoglobins. Coordinated changes have been found in all three protein families mostly within structurally constrained regions. This method works with a varying degree of success depending on the function of the proteins, the range of sequence similarities and the number of sequences considered. By relaxing the criteria for residue selection, the method was adapted to cover a broader range of protein families and to study regions of the proteins having weaker structural constraints. The information derived by these methods provides a general guide for engineering of a large variety of proteins to analyse structure-function rela-tionships. Key words: protein structure/sequence similarities/protein engineering/proteases/haemoglobin