Exploring functionally related enzymes using radially distributed properties of active sites around the reacting points of bound ligands

We showed that radial distribution functions (RDFs), which are associated with the local structural and physicochemical properties of catalytic active sites, are capable of clustering oxidoreductases and transferases by function. The catalytic sites of these enzymes were also characterized using the RDFs. The RDFs provided a measure of the similarity among the catalytic sites, detecting conformational changes caused by mutation of catalytic residues. Furthermore, the RDFs reinforced the classification of enzyme functions based on conventional sequence and structural alignments.Our results demonstrate that the application of RDFs provides advantages in the functional classification of enzymes by providing information about catalytic sites.High-throughput methods for structural genomics have produced an increasing number of protein structures to be solved by X-ray crystallography. The abundance of protein structure information in the Protein Data Bank (PDB) has increased the need and desire for structure-based function prediction [1] and has contributed to structure-based drug design [2]. However, two problems remain regarding the prediction of enzyme function. First, proteins within a superfamily, which are usually expected to share the same catalytic properties, can catalyze different reactions. There are reports that enzymes with 98% sequence identity, such as melamine deaminase and atrazine chlorohydrolase, may catalyze different reactions [3]. Second, two enzymes belonging to different superfamilies or fold classes can catalyze almost identical reactions [4].The function of a protein can be affected by a small number of residues in a localized region of its three-dimensional structure [5]. Moreover, the specific arrangement and conformation of these residues can be crucial to a protein’s function and may be strongly conserved during its evolution, even when the protein sequence and structure change significantly [5]. For example, it was reported that the position