CATH database

Sequence conservation is, in general, much weaker than structural conservation. There are proteins, which are clearly not related in sequence but are closely related in 3D-stmcture and fold, like heamoglobin and myoglobin, which have similar functions. In many proteins, fold elements like 4-helical bundles are repeated. Classifications of known structural folds of proteins are organized in the SCOP or CATH database see e.g., http //scop.mrc-lmb.cam.ac.uk/scop/. 

Orengo, C. A., Pearl, F. M Bray, J. E., Todd, A. E., Martin, A. C., Lo Crane, L. Thornton, J. M. (1999). The CATH Database provides insights into protein structure/function relationships. Nucleic Acids Res 27,275-9. 

Our method of clustering based on a-carbon distances and in turn backbone and side chain torsions has demonstrated the existence of possible structural motifs within well defined linker regions. The method is not quite exhaustive to account for data outside the clusters and its limitadons arise due to non-standard way of defining limits of the clusters. Nevertheless, the method does seem to bring out the stmctural differences among various linkers. Our analyses on mainly -a proteins fiom the CATH database (results not shown here) has resulted in two major clusters of three residue linkers between helices (H-L3-H) and few of the helical proteins have same angle of orientation of helices within a cluster. We are yet to extend this observation to the unique data set of protein chains discussed in this paper. 

Pearl, F. M., C. F. Bennett, J. E. Bray, A. P. Harrison, N. Martin, A. Shepherd, I. Sillitoe, J. Thornton, and C. A. Orengo. 2003. The CATH database An extended protein family resource for structural and functional genomics. Nucleic Acids Res 31 452-5. 

The CATH database of protein structures (http //www. biochem.ucl. ac.uk/bsm/dhs)... 

CATH, FSSP Sequence-structure classification databases... 

Figure 2.10 Examples of schematic diagrams of the type pioneered by Jane Richardson. Diagram (a) illustrates the structure of myoglobin in the same orientation as the computer-drawn diagrams of Figures 2.9b-d. Diagram (b), which is adapted from J. Richardson, illustrates the structure of the enzyme triosephosphate isomerase, determined to 2.5 A resolution in the laboratory of David Phillips, Oxford University. Such diagrams can easily be obtained from databases of protein structures, such as PDB, SCOP or CATH, available on the World Wide Web.

In order to make as much data on the structure and its determination available in the databases, approaches for automated data harvesting are being developed. Structure classification schemes, as implemented for example in the SCOP, CATH, andFSSP databases, elucidate the relationship between protein folds and function and shed light on the evolution of protein domains. 

The SCOP database is curated manually, with the objective of placing proteins in the correct evolutionary framework based on conserved structural features. Two similar enterprises, the CATH (class, architecture, topology, and homologous superfamily) and FSSP (/old classification based on structure-structure alignment of proteins) databases, make use of more automated methods and can provide additional information. 

The CATH protein domain database (http //www.biochem.ucl.ac.uk/bsm/cath) is a hierarchical classification of protein domain structures into evolutionary families and structural groupings depending on sequence and structure similarity (Pearl et al, 2000). The protein domains are classified according to four major levels. 

Fig. 4 (a) The structure of bovine spleen procathepsin B [47] is shown with the active site Cys, Asn and His residues. The PDB coordinates 1QDQ for bovine cath B were obtained from the Structure Database, NCBI. (b) Docking geometry of RAPTA-pentaOH to cat B illustrating the main interactions of the ligand with the residues flanking the active site (reproduced, with modifications, from ref. [28]. The contour map for the hydrophobic field calculated with the sidemap module implemented in Maestro is also shown (transparent). 

S, Johnston C, SiUero A, Thornton J, Orengo C (2005) The CATH domain structure database and related resources Gene3D and DHS provide comprehensive domain family information for genome analysis. Nucleic Acids Res 33 D247-D251... 

Protein-pattern databases cover both motifs or functional domains and secondary structure. We have included the entire InterPro family of databases, as well as BLOCKS, CDD, and a description of patterns found in Swiss-Prot sequences. DSSP, ISSD, PSSD, and CATH are covered in the secondary-structure section. 

Reliable secondary structures can enhance the prediction of higher order protein structure, and to a limited extent, secondary-structure motifs can even suggest specific fold structures. Sometimes these secondary structures provide insight into function. Definition of Secondary Structure of Proteins (DSSP), Integrated Sequence-Structure Database (ISSD), Protein Secondary Structure Database (PSSD), and CATH are covered in this section (see Table 2.2). 

Orengo, C. A., F. M. Pearl, and J. M. Thornton. 2003. The CATH domain structure database. Methods Biochem Anal 44 249-71. 

If the structure you are considering is already in the PDB, then these similarities can be found in a number of databases including SCOP [48] (http //scop.mrc-lmb. cam.ac.uk/scop/index.html), CATH [49] (http //www.biochem.ucl.ac.uk/bsm/cath/ cath.html), and FSSP/Dali [50] (http //ekhidna.biocenter.helsinki.fi/dali/). However, if the structure is not yet in the PDB, you will need to perform your own structure search to compare your structure to all other known structures. In a broad sense, structure searching is similar to sequence searches however, the methods used are very different and quite a bit slower. Some standard methods are Dali [51] (http //ekhidna.biocenter.helsinki.fi/dali/), VAST [52] (http //www.ncbi.nhn.nih.gov/ Structure/VAST/vastsearch.html), and SSM [53] (http //www.ebi.ac.uk/msd/Services. html). 

Templates can be selected using the target sequence as a query for searching protein structure databases [e.g. Brookhaven Protein Data Bank (PDB) http / /www.rcsb.org/pdb/index.html Structural Classification of Proteins (SCOP) scop.mrc-lmb.cam.ac.uk/scop/ DALI www2.ebi.ac.uk/dali/ Class, Architecture, Topology and Homologous superfamily classification at CATH www.biochem.ucl.a-c.uk/bsm/cath/). 

Murzin, A. G., Brenner, S. E., Hubbard, T., and Chothia, C., 1995. SCOP A structural classification of proteins database for the investigation of sequences and structures./. Mol. Biol 247 536-540. Hadley, C., and Jones, D. T., 1999. A systematic comparison of protein structure classification SCOP, CATH and FSSP. Structure Fold. Des. 7 1099-1112. 

CATH Protein structure classification database http //www.biochem.ucl.ac. uk/bsm/cath/... 

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