SH2db

SH2db provides a comprehensive structural database of SH2 domain structures to support comparative structural analysis, sequence alignment, and structure-guided studies of phosphotyrosine-based signaling.

Key Features:

• Comprehensive Structural Data: Houses experimentally determined PDB entries and predicted models from AlphaFold for SH2 domains.
• Generic Residue Numbering Scheme: Employs a generic residue numbering scheme to enable residue-level comparisons across SH2 domain structures.
• Structure-Based Multiple Sequence Alignment: Contains a structure-based multiple sequence alignment for all 120 human wild-type SH2 domain sequences integrating PDB and AlphaFold-derived structures.
• Conserved Structural Framework: Represents the conserved central beta-sheet architecture that partitions the binding surface into phosphotyrosine (pY) and substrate specificity (pY + 3) pockets.

Scientific Applications:

• Drug Discovery: Supports identification of SH2 domain binding sites and design of inhibitors targeting phosphotyrosine (pY) and pY + 3 specificity pockets.
• Structural Biology: Enables analysis of SH2 domain conformational features and functional mechanisms within phosphotyrosine-based signaling pathways.
• Comparative Studies: Facilitates cross-domain comparative analyses, evolutionary studies, and investigations of specificity using the generic residue numbering and structure-based alignments.

Methodology:

Aggregated PDB entries and AlphaFold predicted models, generated a structure-based multiple sequence alignment for 120 human wild-type SH2 domains, and applied a generic residue numbering scheme.