Title:Protein Interaction Domains and Post-Translational Modifications: Structural Features and Drug Discovery Applications
Volume: 27
Issue: 37
关键词:
蛋白质结合模块，翻译后修饰，多肽，小分子，结合位点，结构生物学，药物发现
摘要: Background: Many pathways regarding healthy cells and/or linked to diseases onset and
progression depend on large assemblies including multi-protein complexes. Protein-protein interactions
may occur through a vast array of modules known as Protein Interaction Domains (PIDs).
Objective: This review concerns with PIDs recognizing post-translationally modified peptide sequences
and intends to provide the scientific community with state of art knowledge on their 3D
structures, binding topologies and potential applications in the drug discovery field.
Method: Several databases, such as the Pfam (Protein family), the SMART (Simple Modular Architecture
Research Tool) and the PDB (Protein Data Bank), were searched to look for different domain
families and gain structural information on protein complexes in which particular PIDs are
involved. Recent literature on PIDs and related drug discovery campaigns were retrieved through
Pubmed and analyzed.
Results and Conclusion: PIDs are rather versatile as concerned with their binding preferences.
Many of them recognize specifically only determined amino acid stretches with post-translational
modifications, a few others are able to interact with several post-translationally modified sequences
or with unmodified ones. Many PIDs can be linked to different diseases including cancer. The tremendous
amount of available structural data led to the structure-based design of several molecules
targeting protein-protein interactions mediated by PIDs, including peptides, peptidomimetics and
small compounds. More studies are needed to fully role out, among different families, PIDs that can
be considered reliable therapeutic targets, however, attacking PIDs rather than catalytic domains of a
particular protein may represent a route to obtain selective inhibitors.
