Molecular dynamic simulation reveals the inhibiting impact of Rhein on wild-type and P29S-mutated Rac1.

Autor:	Etebar N; Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran.; Faculty of Pharmacy, Eastern Mediterranean University, Famagusta, Cyprus., Hamidi SH; Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran.; Acharya BM Reddy College of Pharmacy, Rajiv Gandhi University of Health Sciences, Bangalore, India., Naderpour S; Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran.; Faculty of Pharmacy, Eastern Mediterranean University, Famagusta, Cyprus., Abouali O; Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran.; Faculty of Pharmacy, Cyprus International University, Nicosia, Cyprus., Hamidi SH; Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran.; Al-Ameen College of Pharmacy, Rajiv Gandhi University of Health Sciences, Bangalore, India., Hajipour-Verdom B; Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran.; Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran., Zali A; Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Alipour M; Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Rahimzadegan M; Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular biosciences [Front Mol Biosci] 2024 Aug 05; Vol. 11, pp. 1414197. Date of Electronic Publication: 2024 Aug 05 (Print Publication: 2024).
DOI:	10.3389/fmolb.2024.1414197
Abstrakt:	Ras-related C3 botulinum toxin substrate 1 (Rac1) is a small GTPase belonging to the Rho family. It acts as a binary molecular switch regulating several cellular functions, including cell adhesion and migration. Malfunctions due to the P29S mutation in Rac1 increase the stability of the activated form of Rac1. This sustained activation can drive aberrant cellular processes associated with cancer, such as cell proliferation, survival, and migration. Therefore, finding an inhibitor that can inhibit the mutant form of the protein is very important. Rhein, a natural compound with diverse pharmacological properties, has been studied in relation to Rac1. However, specific interactions between Rhein and Rac1 have not been examined. In this study, we investigated the potential of Rhein, a natural compound, as an inhibitor of two forms of Rac1: the wild type and the P29S mutation, using molecular dynamics simulations. Results indicated that the P29S mutation led to structural changes in the Rac1 protein, which resulted in greater accessibility of the Rhein to the active site. In addition, the binding energy of Rhein to mutant Rac1 was more negative than the native protein. Therefore, it seems that the Rhein has a better inhibitory effect on the P29S-mutated form of the Rac1 protein. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Etebar, Hamidi, Naderpour, Abouali, Hamidi, Hajipour-Verdom, Zali, Alipour and Rahimzadegan.)
Databáze:	MEDLINE
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