Mutants and molecular dockings reveal that the primary L-thyroxine binding site in human serum albumin is not the one which can cause familial dysalbuminemic hyperthyroxinemia

Biochimica Et Biophysica Acta
U Kragh-HansenM Otagiri

Abstract

Natural mutations of R218 in human serum albumin (HSA) result in an increased affinity for L-thyroxine and lead to the autosomal dominant condition of familial dysalbuminemic hyperthyroxinemia. Binding was studied by equilibrium dialysis and computer modeling. Ten of 32 other isoforms tested had modified high-affinity hormone binding. L-thyroxine has been reported to bind to four sites (Tr) in HSA; Tr1 and Tr4 are placed in the N-terminal and C-terminal part of the protein, respectively. Site-directed mutagenesis gave new information about all the sites. It is widely assumed that Tr1 is the primary hormone site, and that this site, on a modified form, is responsible for the above syndrome, but the binding experiments with the genetic variants and displacement studies with marker ligands indicated that the primary site is Tr4. This new assignment of the high-affinity site was strongly supported by results of MM-PBSA analyses and by molecular docking performed on relaxed protein structure. However, dockings also revealed that mutating R218 for a smaller amino acid increases the affinity of Tr1 to such an extent that it can become the high-affinity site. Placing the high-affinity binding site (Tr4) and the one which can result in ...Continue Reading

References

Jul 16, 1992·Nature·X M He, D C Carter
Oct 5, 1990·European Journal of Biochemistry·U Kragh-HansenO Sugita
May 1, 1993·Analytical Biochemistry·U Kragh-Hansen
Jul 5, 1994·Proceedings of the National Academy of Sciences of the United States of America·J MadisonF W Putnam
Oct 20, 1999·European Journal of Endocrinology·K T TangL E Braverman
Mar 16, 2000·Thyroid : Official Journal of the American Thyroid Association·G C Schussler
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·N A BakerJ A McCammon
Dec 12, 2001·Biochimica Et Biophysica Acta·U Kragh-HansenP H Jensen
Jul 9, 2002·Journal of Pediatric Endocrinology & Metabolism : JPEM·Theodore W AvRuskinRoy E Weiss
May 14, 2003·Proceedings of the National Academy of Sciences of the United States of America·Isabelle PetitpasStephen Curry
Mar 19, 2004·Journal of Medicinal Chemistry·Richard A FriesnerPeter S Shenkin
Apr 30, 2004·Journal of Computational Chemistry·Junmei WangDavid A Case
Apr 2, 2005·Analytical Biochemistry·Ulrich Kragh-HansenAnders Overgaard Pedersen
Sep 20, 2005·Journal of Molecular Biology·Jamie GhumanStephen Curry
Sep 19, 2006·Journal of Molecular Biology·Ulrich Kragh-HansenMasaki Otagiri
Jan 11, 2007·The Journal of Chemical Physics·Giovanni BussiMichele Parrinello
Jul 8, 2008·Journal of Molecular Biology·Patricia A ZunszainStephen Curry
May 30, 2009·Journal of Chemical Information and Modeling·Jason B CrossChristine Humblet
Mar 30, 2010·Journal of Structural Biology·Kim Langmach HeinPoul Nissen
Apr 22, 2010·Proteins·Kresten Lindorff-LarsenDavid E Shaw
Jul 25, 2012·BMC Research Notes·Alan W Sousa da Silva, Wim F Vranken
Apr 6, 2013·Biochimica Et Biophysica Acta·Ulrich Kragh-HansenTheodore Peters
Apr 13, 2013·Journal of Computer-aided Molecular Design·G Madhavi SastryWoody Sherman
Feb 6, 2014·Thyroid : Official Journal of the American Thyroid Association·Solomon Maximo GreenbergSamuel Refetoff
Mar 22, 2014·The Journal of Clinical Endocrinology and Metabolism·Nadia SchoenmakersKrishna Chatterjee

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Citations

Apr 19, 2016·Clinica Chimica Acta; International Journal of Clinical Chemistry·Stephen O BrennanPeter M George
Jan 26, 2018·Frontiers in Molecular Biosciences·Changhao WangRay Luo
Nov 7, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Lin WangZhaohui Lyu
Apr 14, 2021·Biotechnic & Histochemistry : Official Publication of the Biological Stain Commission·Gökçen BiliciGüven Erbil
Jun 19, 2021·Journal of Pediatric Endocrinology & Metabolism : JPEM·Saygin AbaliSerap Semiz

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