| Autor: |
Ivan Mercurio, Gianluca D’Abrosca, Maria della Valle, Gaetano Malgieri, Roberto Fattorusso, Carla Isernia, Luigi Russo, Sonia Di Gaetano, Emilia Maria Pedone, Luciano Pirone, Annarita Del Gatto, Laura Zaccaro, Domenico Alberga, Michele Saviano, Giuseppe Felice Mangiatordi |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Computational and Structural Biotechnology Journal, Vol 23, Iss , Pp 2001-2010 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2001-0370 |
| DOI: |
10.1016/j.csbj.2024.04.063 |
| Popis: |
In a recent study, we have identified BPH03 as a promising scaffold for the development of compounds aimed at modulating the interaction between PED/PEA15 (Phosphoprotein Enriched in Diabetes/Phosphoprotein Enriched in Astrocytes 15) and PLD1 (phospholipase D1), with potential applications in type II diabetes therapy. PED/PEA15 is known to be overexpressed in certain forms of diabetes, where it binds to PLD1, thereby reducing insulin-stimulated glucose transport. The inhibition of this interaction reestablishes basal glucose transport, indicating PED as a potential target of ligands capable to recover glucose tolerance and insulin sensitivity. In this study, we employ computational methods to provide a detailed description of BPH03 interaction with PED, evidencing the presence of a hidden druggable pocket within its PLD1 binding surface. We also elucidate the conformational changes that occur during PED interaction with BPH03. Moreover, we report new NMR data supporting the in-silico findings and indicating that BPH03 disrupts the PED/PLD1 interface displacing PLD1 from its interaction with PED. Our study represents a significant advancement toward the development of potential therapeutics for the treatment of type II diabetes. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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