Targeting PDZ domains as potential treatment for viral infections, neurodegeneration and cancer.
Targeting PDZ domains as potential treatment for viral infections, neurodegeneration and cancer.
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DOI：
10.1186/s13062-021-00303-9
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发表时间：
2021-10-12
期刊：
影响因子：
5.5
通讯作者：
Toto A
中科院分区：
文献类型：
--
作者：
Nardella C;Visconti L;Malagrinò F;Pagano L;Bufano M;Nalli M;Coluccia A;La Regina G;Silvestri R;Gianni S;Toto A
蛋白质之间的相互作用是细胞生命的基本事件，通常由专门的蛋白质结构域或模块介导。PDZ结构域是最大的一类蛋白质-蛋白质相互作用模块，参与多种细胞途径，如信号转导、细胞-细胞连接、细胞极性和粘附以及蛋白质运输。正因为如此，PDZ结构域功能的失调通常导致病理的发作，从而使该结构域家族成为有趣的药物靶标。在这篇综述文章中，我们提供了一个概述的结构和功能特点的PDZ域及其参与的细胞和分子途径的基础上，不同的人类病理。我们还讨论了一些已经开发的策略，最终目标是劫持或抑制PDZ结构域与其配体的相互作用。由于PDZ结构域的结合选择性通常较低，并且小分子在抑制PDZ结合方面的效率不足，因此该任务特别难以实现，并且仍然需要增加实验努力，以便在体内变得完全可行和成功。
The interaction between proteins is a fundamental event for cellular life that is generally mediated by specialized protein domains or modules. PDZ domains are the largest class of protein–protein interaction modules, involved in several cellular pathways such as signal transduction, cell–cell junctions, cell polarity and adhesion, and protein trafficking. Because of that, dysregulation of PDZ domain function often causes the onset of pathologies, thus making this family of domains an interesting pharmaceutical target. In this review article we provide an overview of the structural and functional features of PDZ domains and their involvement in the cellular and molecular pathways at the basis of different human pathologies. We also discuss some of the strategies that have been developed with the final goal to hijack or inhibit the interaction of PDZ domains with their ligands. Because of the generally low binding selectivity of PDZ domain and the scarce efficiency of small molecules in inhibiting PDZ binding, this task resulted particularly difficult to pursue and still demands increasing experimental efforts in order to become completely feasible and successful in vivo.
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影响因子：
5.2
作者：
Boccuto, Luigi;Lauri, Maria;Schwartz, Charles E.
通讯作者：
Schwartz, Charles E.
影响因子：
4.8
作者：
Chen, Qian;Zou, Junhuang;Yang, Jun
通讯作者：
Yang, Jun
影响因子：
3.7
作者：
Assemat, Emeline;Crost, Emmanuelle;Massey-Harroche, Dominique
通讯作者：
Massey-Harroche, Dominique
影响因子：
8
作者：
Boukerche, H.;Aissaoui, H.;Prevost, C.;Hirbec, H.;Das, S. K.;Su, Z-Z;Sarkar, D.;Fisher, P. B.
通讯作者：
Fisher, P. B.
影响因子：
16.2
作者：
CHO, KO;HUNT, CA;KENNEDY, MB
通讯作者：
KENNEDY, MB