pKa Calculations of GPCRs: Understanding Protonation States in Receptor Activation.
J Chem Inf Model
; 64(17): 6850-6856, 2024 Sep 09.
Article
em En
| MEDLINE
| ID: mdl-39150719
ABSTRACT
The increase in the available G protein-coupled receptor (GPCR) structures has been pivotal in helping to understand their activation process. However, the role of protonation-conformation coupling in GPCR activation still needs to be clarified. We studied the protonation behavior of the highly conserved Asp2.50 residue in five different class A GPCRs (active and inactive conformations) using a linear response approximation (LRA) pKa calculation protocol. We observed consistent differences (1.3 pK units) for the macroscopic pKa values between the inactive and active states of the A2AR and B2AR receptors, indicating the protonation of Asp2.50 during GPCR activation. This process seems to be specific and not conserved, as no differences were observed in the pKa values of the remaining receptors (CB1R, NT1R, and GHSR).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Conformação Proteica
/
Prótons
/
Receptores Acoplados a Proteínas G
Limite:
Humans
Idioma:
En
Revista:
J Chem Inf Model
Assunto da revista:
INFORMATICA MEDICA
/
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Portugal