CPDB: a database of circular permutation in proteins

Abstract

Circular permutation (CP) in a protein can be considered as if its sequence were circularized followed by a creation of termini at a new location. Since the first observation of CP in 1979, a substantial number of studies have concluded that circular permutants (CPs) usually retain native structures and functions, sometimes with increased stability or functional diversity. Although this interesting property has made CP useful in many protein engineering and folding researches, large-scale collections of CP-related information were not available until this study. Here we describe CPDB, the first CP DataBase. The organizational principle of CPDB is a hierarchical categorization in which pairs of circular permutants are grouped into CP clusters, which are further grouped into folds and in turn classes. Additions to CPDB include a useful set of tools and resources for the identification, characterization, comparison and visualization of CP. Besides, several viable CP site prediction methods are implemented and assessed in CPDB. This database can be useful in protein folding and evolution studies, the discovery of novel protein structural and functional relationships, and facilitating the production of new CPs with unique biotechnical or industrial interests. The CPDB database can be accessed at http://sarst.life.nthu.edu.tw/cpdb.

Figure 1.

Various methods provided by CPDB for visualizing CP relationships among proteins. (a) Circularly permutated structure and sequence alignments. Cα atoms of terminal residues of the superimposed structures are shown as balls so that the different locations of termini, which are a property of CP, can be easily recognized. Two proteins are colored very differently. The boundaries between the lighter and darker colors are the positions of CP site. (b) Network view of a CP cluster. A CP cluster usually contains several CP pairs with direct or indirect linkages. Proteins with more complicated CP relationships are placed closer to the center of this network. (c) Star-like map of structural homologs. Query protein is at the center (the blue circle) with its circular permutants (red circles) radiating upwards and linear structural homologs (light blue circles) radiating downwards. Connecting lines are drawn in a way that their lengths are in proportion to the structural diversities (41) between proteins.

Figure 2.

Navigation of the CPDB. (a) Home page, (b) hierarchy browsing page, (c) search results page, (d) structural similarity search tools, (e) literature list page and (f) protein page. See Figure 1a for an example of the alignment pages.