Carboxylic ester hydrolases: Classification and database derived from their primary, secondary, and tertiary...

Area of Science:

• Biochemistry
• Structural Biology
• Bioinformatics

Background:

• Carboxylic ester hydrolases (CEHs) are a diverse group of enzymes with crucial biological roles.
• Previous classification efforts lacked a systematic structural basis.
• Understanding CEH structural diversity is key to enzyme function and engineering.

Purpose of the Study:

• To establish the first systematic structural classification of carboxylic ester hydrolases (CEHs).
• To group CEHs into families and clans based on conserved structural features.
• To create an accessible database for CEH structural information.

Main Methods:

• Utilized multiple sequence alignments, secondary structure analysis, and tertiary structure superpositions for classification.
• Employed the Basic Local Alignment Search Tool (BLAST) to gather CEHs from public databases.
• Analyzed primary, secondary, and tertiary structures to define family and clan relationships.

Main Results:

• Classified CEHs into 91 families, with 36 families grouped into five distinct clans.
• Identified conserved active sites and reaction mechanisms within CEH families.
• Characterized diverse tertiary structures including alpha/beta-hydrolase folds, beta-propellers, and helix bundles.
• The CASTLE database was constructed, containing 321,830 primary and 1378 tertiary structures.

Conclusions:

• The study provides a comprehensive and systematic structural classification of CEHs.
• Structural similarities underpin the grouping of CEHs into families and clans, even with divergent primary sequences.
• The CASTLE database serves as a valuable resource for researchers studying CEHs.