One Amino Acid Controls Which Drugs the Delta Opioid Receptor Prefers
Mutating aspartic acid 95 to asparagine in the delta opioid receptor eliminated selective agonist binding while preserving antagonist binding — pinpointing the key residue for drug selectivity.
Quick Facts
What This Study Found
Asp95Asn mutation in delta opioid receptor eliminated selective high-affinity agonist binding while preserving antagonist binding. Single residue determines agonist selectivity.
Key Numbers
How They Did This
Site-directed mutagenesis of the cloned delta opioid receptor. Mutant and wild-type receptors expressed in cells. Binding assays with selective agonists and antagonists.
Why This Research Matters
Knowing exactly which amino acid controls agonist selectivity enables rational design of new opioid drugs with specific receptor preferences, potentially reducing side effects.
The Bigger Picture
Knowing which single amino acid controls drug selectivity is a goldmine for drug design. It enables scientists to rationally engineer drugs that target specific opioid receptor types, potentially creating painkillers with fewer side effects.
What This Study Doesn't Tell Us
In vitro study using expressed receptors in cell lines. Single point mutation may have additional uncharacterized effects. Does not demonstrate in vivo consequences.
Questions This Raises
- ?Can drugs be designed to interact specifically with Asp95 for enhanced delta selectivity?
- ?Do similar single-residue selectivity switches exist in mu and kappa receptors?
Trust & Context
- Key Stat:
- Single residue Asp95→Asn mutation eliminated selective agonist binding while preserving antagonist binding — one amino acid controls selectivity
- Evidence Grade:
- Moderate — in vitro study with clear mutagenesis results. Strong molecular evidence but functional consequences in vivo not tested.
- Study Age:
- Published in 1993 (33 years ago). This finding has informed decades of opioid receptor structural biology and drug design.
- Original Title:
- A single residue, aspartic acid 95, in the delta opioid receptor specifies selective high affinity agonist binding.
- Published In:
- The Journal of biological chemistry, 268(31), 23055-8 (1993)
- Authors:
- Kong, H(2), Raynor, K(2), Yasuda, K(2), Moe, S T, Portoghese, P S, Bell, G I, Reisine, T
- Database ID:
- RPEP-00268
Evidence Hierarchy
Frequently Asked Questions
Why does one amino acid matter so much?
Opioid receptors are protein structures where drugs fit into a binding pocket. Asp95 sits right in the pocket where agonists bind. Changing it to a slightly different amino acid disrupts the fit for agonists but not antagonists.
How does this help make better drugs?
If scientists know exactly which part of the receptor determines drug selectivity, they can design drugs that fit that specific site perfectly — creating medications that target one opioid receptor type without affecting the others.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-00268APA
Kong, H; Raynor, K; Yasuda, K; Moe, S T; Portoghese, P S; Bell, G I; Reisine, T. (1993). A single residue, aspartic acid 95, in the delta opioid receptor specifies selective high affinity agonist binding.. The Journal of biological chemistry, 268(31), 23055-8.
MLA
Kong, H, et al. "A single residue, aspartic acid 95, in the delta opioid receptor specifies selective high affinity agonist binding.." The Journal of biological chemistry, 1993.
RethinkPeptides
RethinkPeptides Research Database. "A single residue, aspartic acid 95, in the delta opioid rece..." RPEP-00268. Retrieved from https://rethinkpeptides.com/research/kong-1993-a-single-residue-aspartic
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.