The Thiamine diphosphate dependent Enzyme Engineering Database: a tool for the systematic analysis of sequence and...

Area of Science:

• Biochemistry
• Structural Biology
• Enzymology

Background:

• Thiamine diphosphate (ThDP)-dependent enzymes catalyze crucial reactions involving various bond formations and cleavages.
• These enzymes, despite sequence diversity, share conserved pyrophosphate (PP) and pyrimidine (PYR) domains.
• The Thiamine diphosphate (ThDP)-dependent Enzyme Engineering Database (TEED) was developed for systematic comparison of these enzymes.

Purpose of the Study:

• To establish a comprehensive database (TEED) for ThDP-dependent enzymes.
• To enable systematic analysis and comparison of protein sequences and structures.
• To provide a tool for investigating human ThDP-dependent enzymes and their associated genetic variations.

Main Methods:

• Curated a database (TEED) with over 12,000 sequence and 300 structure entries.
• Classified proteins into 8 superfamilies and 63 homologous families.
• Annotated conserved PP and PYR domains for similarity analysis and developed family-specific HMM profiles.

Main Results:

• The TEED database encompasses 12,048 sequence entries and 379 structure entries.
• Proteins are organized into 8 superfamilies and 63 homologous families, with associated alignments and phylogenetic trees.
• Identified 20 human ThDP-dependent proteins and over 40 single nucleotide polymorphisms (SNPs) linked to diseases.

Conclusions:

• The TEED database serves as a valuable navigation and analysis tool for the extensive family of ThDP-dependent enzymes.
• Facilitates research into enzyme function, evolution, and disease associations.
• Supports comparative analysis of protein sequences and structures through annotated domains and family classifications.