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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2002-3-6
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1470-3203
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
1
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
283-8
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11881039-Amino Acid Sequence,
pubmed-meshheading:11881039-Angiotensin Receptor Antagonists,
pubmed-meshheading:11881039-Animals,
pubmed-meshheading:11881039-Benzimidazoles,
pubmed-meshheading:11881039-Binding, Competitive,
pubmed-meshheading:11881039-CHO Cells,
pubmed-meshheading:11881039-Cricetinae,
pubmed-meshheading:11881039-Humans,
pubmed-meshheading:11881039-Ligands,
pubmed-meshheading:11881039-Mutation,
pubmed-meshheading:11881039-Receptor, Angiotensin, Type 1,
pubmed-meshheading:11881039-Receptors, Angiotensin,
pubmed-meshheading:11881039-Tetrazoles
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pubmed:year |
2000
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pubmed:articleTitle |
Lys(199) mutation of the human angiotensin type 1 receptor differentially affects the binding of surmountable and insurmountable non-peptide antagonists.
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pubmed:affiliation |
Department of Molecular and Biochemical Pharmacology, Free University of Brussels, Rode, B-1640, Belgium. ffierens@vub.ac.be
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pubmed:publicationType |
Journal Article
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