Abstract | CONTEXT: PATIENT: RESULTS: The patient's GR gene had a heterozygotic mutation (G-->A) at nucleotide position 2141 (exon 8), which resulted in substitution of arginine by glutamine at amino acid position 714 in the ligand-binding domain (LBD) of the GR alpha. Molecular analysis revealed that the mutant receptor had significantly impaired transactivation activity with a 2-fold reduction in affinity to ligand. It showed attenuated transactivation of the activation function (AF)-2 and reduced binding to a p160 nuclear receptor coactivator. Computer-based structural analysis revealed that replacement of arginine by glutamine at position 714 transmitted a conformational change to the LBD and the AF-2 transactivation surface, resulting in a decreased binding affinity to ligand and to the LXXLL coactivator motif. CONCLUSIONS:
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Authors | Nancy Nader, Bert E Bachrach, Darrell E Hurt, Sonia Gajula, Amy Pittman, Rachel Lescher, Tomoshige Kino |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 95
Issue 5
Pg. 2281-5
(May 2010)
ISSN: 1945-7197 [Electronic] United States |
PMID | 20335448
(Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Intramural)
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Chemical References |
- Glucocorticoids
- Ligands
- Receptors, Glucocorticoid
- Glutamine
- Arginine
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Topics |
- Amino Acid Substitution
- Arginine
(genetics)
- Binding Sites
- Exons
(genetics)
- Female
- Glucocorticoids
(genetics, metabolism)
- Glutamine
(genetics)
- Humans
- Hypoglycemia
(genetics)
- Hypokalemia
(genetics)
- Infant
- Ligands
- Point Mutation
- Polymorphism, Single Nucleotide
- Protein Conformation
- Puberty, Precocious
(genetics)
- Receptors, Glucocorticoid
(chemistry, genetics, metabolism)
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