Efficacy of function specific 3D-motifs in enzyme classification according to their EC-numbers

• Published in: Journal of theoretical biology Vol. 336; pp. 36 - 43
• Main Authors: Rahimi, Amir, Madadkar-Sobhani, Armin, Touserkani, Rouzbeh, Goliaei, Bahram
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 07.11.2013
• Subjects: Active site pattern; active sites; Algorithms; Amino Acid Motifs; ancestry; bioinformatics; Catalytic Domain; Databases, Protein; enzymes; Enzymes - chemistry; Enzymes - classification; Enzymes - metabolism; Function prediction; Function specific motifs; genomics; Homologous enzymes; Models, Molecular; prediction; Spatial arrangement; Function prediction; Homologous enzymes; Spatial arrangement; Function specific motifs; Active site pattern
• ISSN: 0022-5193; 1095-8541; 1095-8541
• DOI: 10.1016/j.jtbi.2013.07.003

Due to the increasing number of protein structures with unknown function originated from structural genomics projects, protein function prediction has become an important subject in bioinformatics. Among diverse function prediction methods, exploring known 3D-motifs, which are associated with functional elements in unknown protein structures is one of the most biologically meaningful methods. Homologous enzymes inherit such motifs in their active sites from common ancestors. However, slight differences in the properties of these motifs, results in variation in the reactions and substrates of the enzymes. In this study, we examined the possibility of discriminating highly related active site patterns according to their EC-numbers by 3D-motifs. For each EC-number, the spatial arrangement of an active site, which has minimum average distance to other active sites with the same function, was selected as a representative 3D-motif. In order to characterize the motifs, various points in active site elements were tested. The results demonstrated the possibility of predicting full EC-number of enzymes by 3D-motifs. However, the discriminating power of 3D-motifs varies among different enzyme families and depends on selecting the appropriate points and features. •The active site patterns of 36 enzyme families containing 144 EC-numbers were studied.•The enzyme families were classified into subfamilies utilizing active site patterns.•Different points in active site residues were tested for defining the 3D-motifs.•The 3D-motifs could discriminate between homologous enzymes with different functions.•The motifs based on alpha carbon coordinates has more consistency than other points.