PAIRED NATURAL CYSTEINE MUTATION MAPPING - AID TO CONSTRAINING MODELSOF PROTEIN TERTIARY STRUCTURE

This paper discusses the benefit of mapping paired cysteine mutation p atterns as a guide to identifying the positions of protein disulfide b onds. This information can facilitate the computer modeling of protein tertiary structure. First, a simple, paired natural-cysteine-mutation map is presented that identifies the positions of putative disulfide bonds in protein families. The method is based on the observation that if, during the process of evolution, a disulfide-bonded cysteine resi due is not conserved, then it is likely that its counterpart will also be mutated. For each target protein, protein databases were searched for the primary amino acid sequences of all known members of distinct protein families. Primary sequence alignment was carried out using Pil eUp algorithms in the GCG package. To search for correlated mutations, we listed only the positions where cysteine residues were highly cons erved and emphasized the mutated residues. In proteins of known three- dimensional structure, a striking pattern of paired cysteine mutations correlated with the positions of known disulfide bridges. For protein s of unknown architecture, the mutation maps showed several positions where disulfide bridging might occur.