CSS

CSS annotates catalytic residues in Protein Data Bank (PDB) structures and provides hand-annotated and homolog-inferred catalytic site annotations (Catalytic Site Atlas, CSA) to support studies in structural biology, enzymology, drug design, protein engineering, and evolutionary analysis.

Key Features:

• Catalytic Residue Annotation: Provides detailed annotations of catalytic residues for enzymes represented in the Protein Data Bank (PDB), including provenance of annotations.
• Dual Annotation Sets: Maintains two annotation types: hand-annotated entries and homologous entries inferred by sequence similarity.
• Hand-Annotated Entries: Curated from primary literature using defined criteria to assign catalytic residues.
• Homologous Entries: Generated by PSI-BLAST and sequence alignment methods against the hand-annotated set to infer catalytic residues in homologous proteins.
• Query Capabilities: Supports lookup of annotations by Swiss-Prot identifiers, Enzyme Commission (EC) numbers, and PDB codes.
• Comprehensive Coverage: Version 1.0 contains 177 hand-annotated entries and 2,608 homologous entries, covering approximately 30% of EC numbers represented in the PDB.
• Regular Updates: Updated monthly to incorporate homologous sites from newly added PDB structures and newly annotated enzymes.

Scientific Applications:

• Enzyme function and mechanism: Enables identification of catalytic residues to inform mechanistic studies and functional annotation.
• Drug design: Provides active-site residue information useful for structure-based inhibitor design.
• Protein engineering: Informs targeted mutagenesis of catalytic residues to alter or probe enzymatic activity.
• Evolutionary studies: Facilitates comparison of catalytic sites across homologs to study conservation and divergence.

Methodology:

Hand-annotated entries are derived from systematic curation of the primary literature; homologous entries are inferred using PSI-BLAST and sequence alignment methods against the hand-annotated set.