Lys(199) mutation of the human angiotensin type 1 receptor differentially affects the binding of surmountable and insurmountable non-peptide antagonists.
| Substance Nomenclature: | 0 (Angiotensin Receptor Antagonists) 0 (Benzimidazoles) 0 (Biphenyl Compounds) 0 (Ligands) 0 (Receptor, Angiotensin, Type 1) 0 (Receptors, Angiotensin) 0 (Tetrazoles) S8Q36MD2XX (candesartan) |
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| Entry Date(s): | Date Created: 20020307 Date Completed: 20020606 Latest Revision: 20211203 |
| Update Code: | 20221213 |
| DOI: | 10.3317/jraas.2000.044 |
| PMID: | 11881039 |
| Autor: | Fierens FL; Department of Molecular and Biochemical Pharmacology, Free University of Brussels, Rode, B-1640, Belgium. ffierens@vub.ac.be, Vanderheyden PM, Gáborik Z, Minh TL, Backer JP, Hunyady L, Ijzerman A, Vauquelin G |
| Jazyk: | angličtina |
| Zdroj: | Journal of the renin-angiotensin-aldosterone system : JRAAS [J Renin Angiotensin Aldosterone Syst] 2000 Sep; Vol. 1 (3), pp. 283-8. |
| DOI: | 10.3317/jraas.2000.044 |
| Abstrakt: | Many slow dissociating (insurmountable) non-peptide angiotensin type 1 receptor (AT1) antagonists contain,besides the acidic biphenyltetrazole substructure of losartan, a second acidic group to stabilise antagonist-receptor complexes. To investigate the involved basic amino-acids of the human AT1-receptor, wild-type and mutant receptors were transiently transfected in CHO-K1 cells and characterised by [3H]candesartan binding. Lys199-->Gln substitution decreased the affinity 45-fold for candesartan (95% insurmountable),18-fold for EXP3174 (70% insurmountable), 10-fold for irbesartan (40% insurmountable) and 5-fold for losartan (surmountable). His256 -->Ala substitution had only minor effects. This suggests that Lys199 is important for the tight binding of non-peptide antagonists. |
| Databáze: | MEDLINE |
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