StrucPTM: a database of structurally validated protein modifications and their conformational variation

Area of Science:

• Biochemistry
• Structural Biology
• Bioinformatics

Background:

• Post-translational modifications (PTMs) are crucial for protein function and regulation, but understanding their structural impact is limited by sequence-centric resources.
• Existing databases often fail to capture how chemical modifications alter protein three-dimensional structures.

Purpose of the Study:

• To develop a comprehensive structural database (StrucPTM) that contextualizes PTM sites within experimentally determined protein structures.
• To provide a foundation for investigating the structural and functional consequences of PTMs.

Main Methods:

• Developed StrucPTM by extracting modified residues directly from Protein Data Bank (PDB) structures using atom-level composition rules.
• Mapped validated PTMs to UniProt entries and characterized modified residues by secondary structure, relative solvent accessibility (RSA), and interface location.
• Grouped homologous protein chains based on sequence identity to distinguish PTM-induced conformational changes from sequence divergence.

Main Results:

• StrucPTM significantly expands coverage of PTM sites compared to annotation-dependent methods.
• The database provides detailed structural context for PTMs, including secondary structure, RSA, and interface localization.
• Homolog-based comparison facilitates the identification of PTM-specific structural alterations.

Conclusions:

• StrucPTM offers a valuable resource for exploring the structural impact of PTMs.
• The database enables researchers to analyze how PTMs influence protein structure, function, and regulation at a structural level.