Lys 199 mutation of the human angiotensin type 1 receptor differentially affects the binding of surmountable and insurmountable non-peptide antagonists
Many slow dissociating (insurmountable) non-peptide angiotensin type 1 receptor (AT 1 ) 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 AT...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publications
2000-09-01
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| Series: | Journal of the Renin-Angiotensin-Aldosterone System |
| Online Access: | https://doi.org/10.3317/jraas.2000.044 |
| _version_ | 1797283678639882240 |
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| author | Frederik LP Fierens Patrick ML Vanderheyden Zsuzsanna Gáborik Tam Le Minh Jean-Paul De Backer László Hunyady Adriaan Ijzerman Georges Vauquelin |
| author_facet | Frederik LP Fierens Patrick ML Vanderheyden Zsuzsanna Gáborik Tam Le Minh Jean-Paul De Backer László Hunyady Adriaan Ijzerman Georges Vauquelin |
| author_sort | Frederik LP Fierens |
| collection | DOAJ |
| description | Many slow dissociating (insurmountable) non-peptide angiotensin type 1 receptor (AT 1 ) 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 AT 1 -receptor, wild-type and mutant receptors were transiently transfected in CHO-K1 cells and characterised by [ 3 H]candesartan binding. Lys 199 → 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). His 256 → Ala substitution had only minor effects. This suggests that Lys 199 is important for the tight binding of non-peptide antagonists. |
| first_indexed | 2024-03-07T17:35:19Z |
| format | Article |
| id | doaj.art-a9ceec2575d64173805c80fd6cbf050a |
| institution | Directory Open Access Journal |
| issn | 1470-3203 |
| language | English |
| last_indexed | 2024-03-07T17:35:19Z |
| publishDate | 2000-09-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Journal of the Renin-Angiotensin-Aldosterone System |
| spelling | doaj.art-a9ceec2575d64173805c80fd6cbf050a2024-03-02T17:10:11ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1470-32032000-09-01110.3317/jraas.2000.044Lys 199 mutation of the human angiotensin type 1 receptor differentially affects the binding of surmountable and insurmountable non-peptide antagonistsFrederik LP FierensPatrick ML VanderheydenZsuzsanna GáborikTam Le MinhJean-Paul De BackerLászló HunyadyAdriaan IjzermanGeorges VauquelinMany slow dissociating (insurmountable) non-peptide angiotensin type 1 receptor (AT 1 ) 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 AT 1 -receptor, wild-type and mutant receptors were transiently transfected in CHO-K1 cells and characterised by [ 3 H]candesartan binding. Lys 199 → 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). His 256 → Ala substitution had only minor effects. This suggests that Lys 199 is important for the tight binding of non-peptide antagonists.https://doi.org/10.3317/jraas.2000.044 |
| spellingShingle | Frederik LP Fierens Patrick ML Vanderheyden Zsuzsanna Gáborik Tam Le Minh Jean-Paul De Backer László Hunyady Adriaan Ijzerman Georges Vauquelin Lys 199 mutation of the human angiotensin type 1 receptor differentially affects the binding of surmountable and insurmountable non-peptide antagonists Journal of the Renin-Angiotensin-Aldosterone System |
| title | Lys 199 mutation of the human angiotensin type 1 receptor differentially affects the binding of surmountable and insurmountable non-peptide antagonists |
| title_full | Lys 199 mutation of the human angiotensin type 1 receptor differentially affects the binding of surmountable and insurmountable non-peptide antagonists |
| title_fullStr | Lys 199 mutation of the human angiotensin type 1 receptor differentially affects the binding of surmountable and insurmountable non-peptide antagonists |
| title_full_unstemmed | Lys 199 mutation of the human angiotensin type 1 receptor differentially affects the binding of surmountable and insurmountable non-peptide antagonists |
| title_short | Lys 199 mutation of the human angiotensin type 1 receptor differentially affects the binding of surmountable and insurmountable non-peptide antagonists |
| title_sort | lys 199 mutation of the human angiotensin type 1 receptor differentially affects the binding of surmountable and insurmountable non peptide antagonists |
| url | https://doi.org/10.3317/jraas.2000.044 |
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