Evaluating Allosteric Perturbations in Cannabinoid Receptor 1 by In Silico Single-Point Mutation
Díaz Sanzo, Óscar (Universitat Autònoma de Barcelona. Institut de Neurociències)
Renault de Barros, Pedro Victor (Universitat Autònoma de Barcelona. Institut de Neurociències)
Giraldo, Jesús (Universitat Autònoma de Barcelona. Institut de Neurociències)

Date:	2022
Abstract:	Cannabinoid receptor 1 (CB1) is a promising drug target involved in many physiological processes. Using atomistic molecular dynamics (MD) simulations, we examined the structural effect of F237L mutation on CB1, a mutation that has qualitatively similar effects to allosteric ligand ORG27569 binding. This mutation showed a global effect on CB1 conformations. Among the observed effects, TM6 outward movement and the conformational change of the NPxxY motif upon receptor activation by CB1 agonist CP55940 were hindered compared to wt CB1. Within the orthosteric binding site, CP55940 interactions with CB1 were altered. Our results revealed that allosteric perturbations introduced by the mutation had a global impact on receptor conformations, suggesting that the mutation site is a key region for allosteric modulation in CB1.
Grants:	European Commission 848068 Agencia Estatal de Investigación PID2020-119136RB-I00
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	ACS omega, Vol. 7 (october 2022) , p. 37873-37884, ISSN 2470-1343

DOI: 10.1021/acsomega.2c04980
PMID: 36312415

12 p, 5.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles