Extending CATH: increasing coverage of the protein structure universe and linking structure with function

Abstract

CATH version 3.3 (class, architecture, topology, homology) contains 128,688 domains, 2386 homologous superfamilies and 1233 fold groups, and reflects a major focus on classifying structural genomics (SG) structures and transmembrane proteins, both of which are likely to add structural novelty to the database and therefore increase the coverage of protein fold space within CATH. For CATH version 3.4 we have significantly improved the presentation of sequence information and associated functional information for CATH superfamilies. The CATH superfamily pages now reflect both the functional and structural diversity within the superfamily and include structural alignments of close and distant relatives within the superfamily, annotated with functional information and details of conserved residues. A significantly more efficient search function for CATH has been established by implementing the search server Solr (http://lucene.apache.org/solr/). The CATH v3.4 webpages have been built using the Catalyst web framework.

Figure 1.

‘CATHerine wheels’. Segments are coloured according to class, namely pink (mainly α), yellow (mainly β), green (αβ) and brown (little secondary structure). The size of each of the segments represents the proportion of structures within any given architecture (inner circle) or fold group (outer circle). (a) The distribution of all non-homologous structures (2386) within CATH v3.3. Superfolds are represented as MOLSCRIPTS adjacent to the wheel. (b) The distribution of the 223 new non-homologous structures in CATH v3.3 (when compared with CATH v3.2).

Figure 2.

Snapshot of superfamily page for CATH v3.4. Keywords giving information on the functions associated with the superfamily are listed at the top of the page. The smallest and largest domain in the family are displayed to highlight the structural diversity within the family. Pie charts showing the distribution of unique functional terms obtained from Gene3D (FunCAT, KEGG pathways and GO terms) are also displayed; selecting one of these pie charts will take a user to a new functional annotation page giving more information (for example, http://beta.cathdb.info/cathnode/3.40.50.720/function).

Figure 3.

Correlation between the degree of structural diversity across a superfamily, measured by the number of close structural clusters and population of the superfamily, in terms of number of sequence clusters (at 30% identity) in the genomes.

Figure 4.

Superfamily comparison plot. Interactive plot which allows the user to compare the structural and functional features of all the superfamilies in CATH though the selection of pull-down menus. The plot displayed here is showing the number of domains for each superfamily against sequence diversity (see http://beta.cathdb.info/cathnode/3.40.50.720/statistics for interactive plot).

Figure 5.

Snapshot of the multiple structural alignment viewer to be released as part of CATH v3.4. Catalytic and ligand binding residues are retrieved from Wssas and annotated in the alignment. 3D images of superimposed or single domain structures are displayed and annotated in the same way as the multiple structural alignment.