The Catalytic Site Atlas 2.0: cataloging catalytic sites and residues identified in enzymes

Abstract

Understanding which are the catalytic residues in an enzyme and what function they perform is crucial to many biology studies, particularly those leading to new therapeutics and enzyme design. The original version of the Catalytic Site Atlas (CSA) (http://www.ebi.ac.uk/thornton-srv/databases/CSA) published in 2004, which catalogs the residues involved in enzyme catalysis in experimentally determined protein structures, had only 177 curated entries and employed a simplistic approach to expanding these annotations to homologous enzyme structures. Here we present a new version of the CSA (CSA 2.0), which greatly expands the number of both curated (968) and automatically annotated catalytic sites in enzyme structures, utilizing a new method for annotation transfer. The curated entries are used, along with the variation in residue type from the sequence comparison, to generate 3D templates of the catalytic sites, which in turn can be used to find catalytic sites in new structures. To ease the transfer of CSA annotations to other resources a new ontology has been developed: the Enzyme Mechanism Ontology, which has permitted the transfer of annotations to Mechanism, Annotation and Classification in Enzymes (MACiE) and UniProt Knowledge Base (UniProtKB) resources. The CSA database schema has been re-designed and both the CSA data and search capabilities are presented in a new modern web interface.

Figure 1.

Overview of data presented for a CSA-curated entry. Meta-data descriptors such as enzyme name and species as well as internal links to find entries in the CSA that share properties along with links to external web resources are shown in a table (A). A 3D viewer (B) displays the enzyme structure, highlighting each of the catalytic sites (from a pull-down menu) in red. A free-text report of the overall reaction and mechanism are provided (C) with a reaction diagram marked up with groups conserved across the reaction and bond changes. (D) Shows the annotations held for each catalytic residues in each catalytic site.

Figure 2.

The database schema for the CSA. Relationships between tables are shown. The data are stored in a MySQL database.

Figure 3.

E.C. coverage in the CSA. The Enzyme Commission classification of all E.C. codes classified by the Enzyme Commission rendered as a rooted tree. Each major class is labeled with (i) Oxidoreductases, (ii) Transferases, (iii) Hydrolases, (iv) Lyases, (v) Isomerases and (vi) Ligases. Each E.C. number in the CSA is colored red, with all major classes and subclasses present and most of the sub-subclasses.