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PDZ Domains as Drug Targets
Author(s) -
Christensen Nikolaj R.,
Čalyševa Jelena,
Fernandes Eduardo F. A.,
Lüchow Susanne,
Clemmensen Louise S.,
HaugaardKedström Linda M.,
Strømgaard Kristian
Publication year - 2019
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.201800143
Subject(s) - pdz domain , interactome , transmembrane protein , drug discovery , postsynaptic density , microbiology and biotechnology , biology , extracellular , receptor , bioinformatics , biochemistry , postsynaptic potential , gene
Protein–protein interactions within protein networks shape the human interactome, which often is promoted by specialized protein interaction modules, such as the postsynaptic density‐95 (PSD‐95), discs‐large, zona occludens 1 (ZO‐1) (PDZ) domains. PDZ domains play a role in several cellular functions, from cell–cell communication and polarization, to regulation of protein transport and protein metabolism. PDZ domain proteins are also crucial in the formation and stability of protein complexes, establishing an important bridge between extracellular stimuli detected by transmembrane receptors and intracellular responses. PDZ domains have been suggested as promising drug targets in several diseases, ranging from neurological and oncological disorders to viral infections. In this review, the authors describe structural and genetic aspects of PDZ‐containing proteins and discuss the current status of the development of small‐molecule and peptide modulators of PDZ domains. An overview of potential new therapeutic interventions in PDZ‐mediated protein networks is also provided.