دورية أكاديمية
أعرض في EDS

Molecular interactions between a diphenyl scaffold and PED/PEA15: Implications for type II diabetes therapeutics targeting PED/PEA15 - Phospholipase D1 interaction.

التفاصيل البيبلوغرافية
العنوان: Molecular interactions between a diphenyl scaffold and PED/PEA15: Implications for type II diabetes therapeutics targeting PED/PEA15 - Phospholipase D1 interaction.
المؤلفون: Mercurio I; Institute of Crystallography, CNR, Via Amendola 122/o, 70126 Bari, Italy.; Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Via Vivaldi 43, 81100 Caserta, Italy., D'Abrosca G; Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy.; Institute of Crystallography, CNR, Via Vivaldi 43, 81100, Caserta, Italy., Della Valle M; Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Via Vivaldi 43, 81100 Caserta, Italy., Malgieri G; Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Via Vivaldi 43, 81100 Caserta, Italy., Fattorusso R; Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Via Vivaldi 43, 81100 Caserta, Italy., Isernia C; Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Via Vivaldi 43, 81100 Caserta, Italy., Russo L; Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Via Vivaldi 43, 81100 Caserta, Italy., Di Gaetano S; Institute of Biostructures and Bioimaging, CNR, Via P. Castellino 111, 80131 Naples, Italy., Pedone EM; Institute of Biostructures and Bioimaging, CNR, Via P. Castellino 111, 80131 Naples, Italy., Pirone L; Institute of Biostructures and Bioimaging, CNR, Via P. Castellino 111, 80131 Naples, Italy., Del Gatto A; Institute of Biostructures and Bioimaging, CNR, Via P. Castellino 111, 80131 Naples, Italy., Zaccaro L; Institute of Biostructures and Bioimaging, CNR, Via P. Castellino 111, 80131 Naples, Italy., Alberga D; Institute of Crystallography, CNR, Via Amendola 122/o, 70126 Bari, Italy., Saviano M; Institute of Crystallography, CNR, Via Vivaldi 43, 81100, Caserta, Italy., Mangiatordi GF; Institute of Crystallography, CNR, Via Amendola 122/o, 70126 Bari, Italy.
المصدر: Computational and structural biotechnology journal [Comput Struct Biotechnol J] 2024 May 04; Vol. 23, pp. 2001-2010. Date of Electronic Publication: 2024 May 04 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology Country of Publication: Netherlands NLM ID: 101585369 Publication Model: eCollection Cited Medium: Print ISSN: 2001-0370 (Print) Linking ISSN: 20010370 NLM ISO Abbreviation: Comput Struct Biotechnol J Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology
Original Publication: Gothenburg, Sweden : Research Network of Computational and Structural Biotechnology
مستخلص: 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.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2024 The Authors.)
References: J Med Chem. 2006 Oct 19;49(21):6177-96. (PMID: 17034125)
J Med Chem. 2004 Mar 25;47(7):1739-49. (PMID: 15027865)
Chem Biol Drug Des. 2007 Feb;69(2):146-8. (PMID: 17381729)
ACS Chem Biol. 2021 Dec 17;16(12):2798-2807. (PMID: 34825823)
Expert Opin Drug Discov. 2015 May;10(5):449-61. (PMID: 25835573)
Mol Biosyst. 2010 Oct;6(10):2039-48. (PMID: 20714510)
Am J Physiol Endocrinol Metab. 2009 Sep;297(3):E592-601. (PMID: 19531639)
Protein Expr Purif. 2008 Jun;59(2):302-8. (PMID: 18420420)
Oncogene. 1999 Aug 5;18(31):4409-15. (PMID: 10442631)
J Biol Chem. 2008 Aug 1;283(31):21769-78. (PMID: 18541525)
J Comput Chem. 2005 Jul 15;26(9):915-31. (PMID: 15841474)
J Chem Theory Comput. 2021 Nov 9;17(11):7106-7119. (PMID: 34592101)
Expert Opin Ther Targets. 2017 Jun;21(6):571-581. (PMID: 28395542)
Dev Cell. 2001 Aug;1(2):239-50. (PMID: 11702783)
J Neurochem. 1998 Sep;71(3):1307-14. (PMID: 9721757)
J Neurochem. 1995 Mar;64(3):1016-25. (PMID: 7861130)
Int J Mol Sci. 2019 Jan 17;20(2):. (PMID: 30658393)
Sci Rep. 2022 Jan 7;12(1):116. (PMID: 34997083)
J Chem Inf Model. 2009 Feb;49(2):377-89. (PMID: 19434839)
Science. 2007 Feb 16;315(5814):972-6. (PMID: 17218491)
J Neurosci. 1999 Oct 1;19(19):8244-51. (PMID: 10493725)
Bioinformatics. 2015 Apr 15;31(8):1325-7. (PMID: 25505092)
EMBO J. 2002 Dec 2;21(23):6494-504. (PMID: 12456656)
J Biol Chem. 1993 Mar 15;268(8):5911-20. (PMID: 8449955)
J Comput Aided Mol Des. 2013 Mar;27(3):221-34. (PMID: 23579614)
Nat Rev Drug Discov. 2004 Apr;3(4):301-17. (PMID: 15060526)
Biochim Biophys Acta. 2012 Dec;1824(12):1382-93. (PMID: 22820249)
Biochem Biophys Res Commun. 2012 Jul 20;424(1):141-6. (PMID: 22732408)
Biochim Biophys Acta. 2013 Aug;1834(8):1572-80. (PMID: 23608947)
J Chem Theory Comput. 2021 Jul 13;17(7):4291-4300. (PMID: 34096718)
Phys Rev A Gen Phys. 1985 Mar;31(3):1695-1697. (PMID: 9895674)
J Med Chem. 2006 Jan 26;49(2):534-53. (PMID: 16420040)
Prog Nucl Magn Reson Spectrosc. 2013 Aug;73:1-16. (PMID: 23962882)
Diabetes. 2007 Mar;56(3):622-33. (PMID: 17327429)
Mol Cell Biol. 2004 Jun;24(11):5005-15. (PMID: 15143191)
J Biol Chem. 1996 Jun 21;271(25):14800-6. (PMID: 8662970)
Biochemistry. 2007 Aug 14;46(32):9187-98. (PMID: 17658892)
Mol Cell Biol. 2003 Jul;23(13):4511-21. (PMID: 12808093)
J Biol Chem. 2002 Jul 12;277(28):25020-5. (PMID: 11976344)
Nat Commun. 2013;4:1681. (PMID: 23575685)
Diabetologia. 2006 Dec;49(12):3058-66. (PMID: 17021921)
Sci Rep. 2015 Sep 24;5:14456. (PMID: 26399546)
EMBO J. 1998 Jul 15;17(14):3858-66. (PMID: 9670003)
Mol Biol Cell. 2000 Sep;11(9):2863-72. (PMID: 10982386)
J Biol Chem. 2000 Nov 10;275(45):35224-32. (PMID: 10926929)
J Med Chem. 2004 Mar 25;47(7):1750-9. (PMID: 15027866)
فهرسة مساهمة: Keywords: Cavity mapping; Molecular Dynamics; Nuclear Magnetic Resonance; Phosphoprotein Enriched in Diabetes/Phosphoprotein Enriched in Astrocytes 15; Type II diabetes
تواريخ الأحداث: Date Created: 20240521 Latest Revision: 20240522
رمز التحديث: 20240522
مُعرف محوري في PubMed: PMC11103223
DOI: 10.1016/j.csbj.2024.04.063
PMID: 38770160
قاعدة البيانات: MEDLINE
الوصف
تدمد:2001-0370
DOI:10.1016/j.csbj.2024.04.063