PAR-3D: a server to predict protein active site residues

Abstract

PAR-3D (http://sunserver.cdfd.org.in:8080/protease/PAR_3D/index.html) is a web-based tool that exploits the fact that relative juxtaposition of active site residues is a conserved feature in functionally related protein families. The server uses previously calculated and stored values of geometrical parameters of a set of known proteins (training set) for prediction of active site residues in a query protein structure. PAR-3D stores motifs for different classes of proteases, the ten glycolytic pathway enzymes and metal-binding sites. The server accepts the structures in the pdb format. The first step during the prediction is the extraction of probable active site residues from the query structure. Spatial arrangement of the probable active site residues is then determined in terms of geometrical parameters. These are compared with stored geometries of the different motifs. Its speed and efficiency make it a beneficial tool for structural genomics projects, especially when the biochemical function of the protein has not been characterized.

Sequence and Structural Features of Enzymes and their Active Sites by EC Class

“…17 Whilst these properties may be useful for identifying active-site residues, the features were not used to differentiate between different enzyme functions. Similarly, numerous other studies have used features ranging from geometry-based features 18,19 to electrostatic 20,21 and chemical features 22,23 to identify enzyme active sites. However, as yet, these features have not been used to distinguish active sites of different EC classes.…”

Computational tools for the synthetic design of biochemical pathways

“…If certain active site residues are known to be essential for this activity, their presence can be verified for the entries in multiple-sequence alignments of the selected branches. Alternatively, active sites can first be predicted ab initio on the basis of sequence conservation and/or structural information 65,66 . If the desired parts are individual genes, candidates can be identified by a simple BLAST search and analysed according to their phylogeny and active site residues in the same fashion as described above.…”

The use of evolutionary patterns in protein annotation

“…A matched protein may then potentially perform the function associated with the template 47 . Several methods, including FunClust 48 , GASPS 49 , SuMo 50 , PAR-3D 51 , and PINTS 52 follow this strategy. They typically rely on a source of structural motifs that are functionally relevant, such as The Catalytic Site Atlas 53 database, which compiles templates for enzyme activity taken from the experimental literature.…”