| Literature DB >> 26091169 |
Eyal Vardy1, Maria F Sassano1, Andrew J Rennekamp2, Wesley K Kroeze1, Philip D Mosier3, Richard B Westkaemper3, Craig W Stevens4, Vsevolod Katritch5, Raymond C Stevens5, Randall T Peterson2, Bryan L Roth6.
Abstract
It has been suggested that the evolution of vertebrate opioid receptors (ORs) follow a vector of increased functionality. Here, we test this idea by comparing human and frog ORs. Interestingly, some of the most potent opioid peptides known have been isolated from amphibian skin secretions. Here we show that such peptides (dermorphin and deltorphin) are highly potent in the human receptors and inactive in frog ORs. The molecular basis for the insensitivity of the frog ORs to these peptides was studied using chimeras and molecular modeling. The insensitivity of the delta OR (DOR) to deltorphin was due to variation of a single amino acid, Trp7.35, which is a leucine in mammalian DORs. Notably, Trp7.35 is completely conserved in all known DOR sequences from lamprey, fish, and amphibians. The deltorphin-insensitive phenotype was verified in fish. Our results provide a molecular explanation for the species selectivity of skin-derived opioid peptides.Entities:
Mesh：
Substances：
Year: 2015 PMID： 26091169 PMCID： PMC4507497 DOI： 10.1016/j.chembiol.2015.05.012
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521