Document Detail


Mutations in a specific human serum albumin thyroxine binding site define the structural basis of familial dysalbuminemic hyperthyroxinemia.
MedLine Citation:
PMID:  8702585     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The familial dysalbuminemic hyperthyroxinemia (FDH) phenotype results from a natural human serum albumin (HSA) mutant with histidine instead of arginine at amino acid position 218. This mutation results in an enhanced affinity for thyroxine. Site-directed mutagenesis and a yeast protein expression system were used to synthesize wild type HSA and FDH HSA as well as several other HSA mutants. Studies on the binding of thyroxine to these HSA species using equilibrium dialysis and quenching of tryptophan 214 fluorescence suggest that the FDH mutation affects a single thyroxine binding site located in the 2A subdomain of HSA. Site-directed mutagenesis of HSA and thyroxine analogs were used to obtain information about the mechanism of thyroxine binding to both wild type and FDH HSA. These studies suggest that the guanidino group of arginine at amino acid position 218 in wild type HSA is involved in an unfavorable binding interaction with the amino group of thyroxine, whereas histidine at amino acid position 218 in FDH HSA is involved in a favorable binding interaction with thyroxine. Neither arginine at amino acid position 222 nor tryptophan at amino acid position 214 appears to favorably influence the binding of thyroxine to wild type HSA.
Authors:
C E Petersen; C E Ha; D M Jameson; N V Bhagavan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  271     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1996 Aug 
Date Detail:
Created Date:  1996-09-16     Completed Date:  1996-09-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  19110-7     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Biophysics, University of Hawaii, Honolulu, Hawaii 96822, USA.
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MeSH Terms
Descriptor/Qualifier:
Binding Sites
Humans
Hyperlipidemias / genetics,  metabolism*
Hyperthyroxinemia / genetics,  metabolism*
Recombinant Proteins / genetics,  metabolism
Serum Albumin / genetics,  metabolism*
Thyroxine / metabolism*
Chemical
Reg. No./Substance:
0/Recombinant Proteins; 0/Serum Albumin; 7488-70-2/Thyroxine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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