Functional differences in the mu opioid receptor SNP 118A>G are dependent on receptor splice-variant and agonist-specific recruitment of β-arrestin.

ABSTRACT: The OPRM1 gene codes for the mu opioid receptor (MOR) and polymorphisms are associated with complex patient clinical responses. The most studied single nucleotide polymorphism (SNP) in OPRM1 is adenine (A) substituted by guanine (G) at position 118 (118A>G, rs1799971) leading to a substitution of asparagine (Asn) for aspartic acid (Asp) at position 40 in the N terminus of the resulting protein. To date, no structural explanation for the associated clinical responses resulting from the 118A>G polymorphism has been proposed. We utilized computational modeling paired with functional cellular assays to predict unstructured N- and C-terminal regions of MOR-1. Using molecular docking and post-docking energy minimizations with morphine, we show that the extracellular substitution of Asn at positi

SUBMITTER: Patrick C 

PROVIDER: S-EPMC11310404 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature