MEROPS

MEROPS classifies and catalogs peptidases, their substrates, and inhibitors to provide a hierarchical and evidence-based resource for peptidase specificity, active sites, structural data, and comparative genomics.

Key Features:

• Hierarchical Classification: Peptidases and protein inhibitors are organized into protein species, families, and clans with detailed information attached at each level.
• Peptidase Specificity Identification: Substrate cleavage specificity and inhibitor interactions are recorded, including a collection of over 39,000 known cleavage sites in proteins, peptides, and synthetic substrates and annotations of cleavage-site conservation.
• Expanded Scope: The dataset includes proteolytic enzymes beyond traditional peptidases to broaden coverage across biological contexts.
• Orthologue Detection: Special identifiers for peptidases from model organisms facilitate detection and cross-species mapping of orthologues.
• Active-Site Analysis: Peptidase summaries include tables of predicted active-site residue positions, metal ligand positions, and domain ranges in orthologues.
• Structural Data: Tertiary structures of peptidases and surface representations are included alongside sequence-based annotations.
• Indexing and Interaction Tables: Indexes for gene names and peptidase substrates, comprehensive peptidase–inhibitor interaction tables including small-molecule inhibitors, catalogs of known cleavage sites per substrate, and tables of substrate-binding preferences derived from combinatorial peptide libraries are provided.
• Genomic Analysis: Tools and datasets support analysis of significant gains and losses of peptidase genes across species using complete genome data.

Scientific Applications:

• Enzyme function annotation: Support for assigning and comparing peptidase functions across species using hierarchical classifications and active-site annotations.
• Substrate specificity and cleavage-site studies: Mapping of cleavage sites and substrate-binding preferences to investigate specificity and conservation.
• Inhibitor interaction profiling: Compilation of peptidase–inhibitor interactions, including small-molecule inhibitors, to inform inhibitor design and mechanistic studies.
• Comparative and evolutionary genomics: Detection of orthologues and analysis of gene gains and losses to study peptidase evolution across complete genomes.
• Structural and functional analysis: Integration of predicted active sites, metal ligands, domain ranges, and tertiary structures to support structural interpretation of catalytic mechanisms.
• Therapeutic target research: Aggregation of specificity, inhibitor, and structural data to aid identification and characterization of potential therapeutic targets.

Methodology:

Hierarchical classification of homologous sets into protein species, families, and clans; curation and cataloging of over 39,000 cleavage sites in proteins, peptides, and synthetic substrates; assignment of special identifiers for model-organism peptidases for orthologue detection; prediction and tabulation of active-site residue positions, metal ligand positions, and domain ranges in orthologues; compilation of substrate-binding preference tables from combinatorial peptide library data; indexing of gene names and substrates; and comparative genomic analyses of peptidase gene gains and losses across complete genomes.