Identification of Functional Diversity in the Enolase Superfamily Proteins

Abstract

The Escherichia coli K12 genome is a widely studied model system. The members of the Enolase superfamily encoded by E.coli catalyze mechanistically diverse reactions that are initiated by base-assisted abstraction of the ┙-proton of a carboxylate anion substrate to form an enodiolate intermediate (Patricia C ,1996). Six of the eight members of the Enolase superfamily encoded by the Escherichia coli K-12 genome have known functions (John F, 2008). The members share a conserved tertiary structure with a two-domain architecture, in which three carboxylate ligands for the Mg2+ ion as well as the acid/base catalysts are located at the C-terminal ends of the ┚-strands in a (┚/┙)7┚-barrel [modified (┚/┙)8or TIMbarrel] domain and the specificity-determining residues are located in an N-terminal ┙+┚ capping domain. The rapid accumulation of data has led to an extraordinary problem of redundancy, which must be confronted in almost any type of statistical analysis. An important goal of bioinformatics is to use the vast and heterogeneous biological data to extract patterns and make discoveries that bring to light the ‘‘unifying’’ principles in biology. (Kaiser Jamil, 2008)Because these patterns can be obscured by bias in the data, we approach the problem of redundancy by appealing to a well known unifying principle in biology, evolution. Bioinformatics has developed as a data-driven science with a primary focus on storing and accessing the vast and exponentially growing amount of sequence and structure data (Gerlt JA, 2005) Protein sequences and their three-dimensional structures are successful descendants of evolutionary process. Proteins might have considerable structural similarities even when no evolutionary relationship of their sequences can be detected (Anurag Sethi, 2005). This property is often referred to as the proteins sharing only a ‘‘fold”. Of course, there are also sequences of common origin in each fold, called a ‘‘superfamily”, and in them groups of sequences with clear similarities, are designated as ‘‘family”. The concept of protein superfamily was introduced by Margaret Dayholff in the 1970 and was used to partition the protein sequence databases based on evolutionary consideration