Molecular basis for the different binding properties of benzodiazepines to human and bovine peripheral-type benzodiazepine receptors
| Autor: | Roseli C. Farges, Pascual Ferrara, Gérard Le Fur, Evelyne Joseph-Liauzun, David Shire, Daniel Caput, Gérard Loison |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
PK-11195
Stereochemistry Recombinant Fusion Proteins Molecular Sequence Data Biophysics Ro5-4864 Biochemistry law.invention Benzodiazepines chemistry.chemical_compound Species Specificity Structural Biology law Mitochondrial receptor Genetics Animals Humans Amino Acid Sequence Receptor Molecular Biology Peptide sequence PK11195 chemistry.chemical_classification GABAA receptor Cell Biology Receptors GABA-A In vitro Amino acid chemistry Recombinant DNA Cattle Chimaeric Recombinant yeast |
| Zdroj: | FEBS Letters. 335:305-308 |
| ISSN: | 0014-5793 |
| DOI: | 10.1016/0014-5793(93)80407-l |
| Popis: | The 18 kDa peripheral benzodiazepine receptor (PBR) can be labelled by benzodiazepines, such as Ro5-4864, and isoquinoline carboxamides such as PK11195. These two compounds are reversible competitive inhibitors of each other. However, while the binding affinity of Ro5-4864 varies enormously across species, PK11195 always displays high affinity, suggesting that their binding domains are overlapping but not identical. We report here that recombinant human and bovine PBR produced in yeast, a microorganism devoid of endogenous PBR, can be labelled with [3H]PK11195, but only the human receptor can be labelled with [3H]Ro5-4864. Furthermore, we identified, through the binding analysis of human-bovine chimaeric receptors, a region near the C-terminal end of the PBR, with only five non-conserved amino acids between human and bovine sequences, as responsible for the difference in high affinity binding of Ro5-4864 to the two receptors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text