|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
5476
|
|
pubmed:dateCreated |
2000-7-28
|
|
pubmed:abstractText |
Hypertension and pregnancy-related hypertension are major public health problems of largely unknown causes. We describe a mutation in the mineralocorticoid receptor (MR), S810L, that causes early-onset hypertension that is markedly exacerbated in pregnancy. This mutation results in constitutive MR activity and alters receptor specificity, with progesterone and other steroids lacking 21-hydroxyl groups, normally MR antagonists, becoming potent agonists. Structural and biochemical studies indicate that the mutation results in the gain of a van der Waals interaction between helix 5 and helix 3 that substitutes for interaction of the steroid 21-hydroxyl group with helix 3 in the wild-type receptor. This helix 5-helix 3 interaction is highly conserved among diverse nuclear hormone receptors, suggesting its general role in receptor activation.
|
|
pubmed:commentsCorrections |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jul
|
|
pubmed:issn |
0036-8075
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
7
|
|
pubmed:volume |
289
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
119-23
|
|
pubmed:dateRevised |
2007-3-19
|
|
pubmed:meshHeading |
pubmed-meshheading:10884226-Adolescent,
pubmed-meshheading:10884226-Aldosterone,
pubmed-meshheading:10884226-Amino Acid Sequence,
pubmed-meshheading:10884226-Amino Acid Substitution,
pubmed-meshheading:10884226-Base Sequence,
pubmed-meshheading:10884226-Binding, Competitive,
pubmed-meshheading:10884226-Dimerization,
pubmed-meshheading:10884226-Female,
pubmed-meshheading:10884226-Heterozygote,
pubmed-meshheading:10884226-Humans,
pubmed-meshheading:10884226-Hypertension,
pubmed-meshheading:10884226-Male,
pubmed-meshheading:10884226-Models, Molecular,
pubmed-meshheading:10884226-Molecular Sequence Data,
pubmed-meshheading:10884226-Pedigree,
pubmed-meshheading:10884226-Point Mutation,
pubmed-meshheading:10884226-Pregnancy,
pubmed-meshheading:10884226-Pregnancy Complications, Cardiovascular,
pubmed-meshheading:10884226-Progesterone,
pubmed-meshheading:10884226-Protein Conformation,
pubmed-meshheading:10884226-Protein Structure, Secondary,
pubmed-meshheading:10884226-Receptors, Mineralocorticoid,
pubmed-meshheading:10884226-Receptors, Steroid,
pubmed-meshheading:10884226-Steroids
|
|
pubmed:year |
2000
|
|
pubmed:articleTitle |
Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy.
|
|
pubmed:affiliation |
Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, Boyer Center for Molecular Medicine, Room 154, 295 Congress Avenue, New Haven, CT 06510, USA.
|
|
pubmed:publicationType |
Journal Article,
Comment,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
