Structure of human plasma prealbumin at 2.5 A resolution

Blake, C. C. F.; Geisow, Michael J.; Swan, I.D.A.; Rérat, C.; Rérat, Berthe

doi:10.1016/0022-2836(74)90291-5

Cited by 258 publications

(64 citation statements)

References 21 publications

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“…Because of this stutistical disorder intrinsic in the space-group symmetry, a detailed rnodel for the modc of binding is difficult to obtain. The same limitations have been encountered previously in the case of the deterinination of the crystal slructures ol' corriplexcs ul' transthyretin with thyroxinc m d other ligands ( Blake et al, 1974;Wo.jtcziik et al, 1992, 1!193). It is importnnt to notice that the electron density for the two crystallographically independent site.…”

Section: Resultsmentioning

confidence: 61%

Crystal Structure of the Transthyretin–Retinoic‐Acid Complex

Zanotti

D’Acunto

Malpeli

et al. 1995

European Journal of Biochemistry

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Retinoids are quite insoluble and chemically unstable compounds in thc aqucous mcdium, such that natural retinoids nccd to be bound to specific retinoid-binding protcins to be protected, solubilized and transported in body fluids. All-tmns retilioic acid exhibits a relatively high affinity for thyroxine-binding transthyretin irz vitm and this protein is a good candidate for the transport of retinoic acid adn~iniskred us pharmacological or antitumor agent. To dcfitic structural features esseniial for the recognition by transthyrctin of a ligand which is structurally unrclatcd to thyroxine, we have cocrysiallized humun transthyrctin with retinoic acid and deleiinincd its structure at 0.18-nrri tesulution. The retinoid fits into thc two chemically identical thyroxine-binding sites, which are located in the ccntral channcl that rutis through the tetranieric transthyretin. The cyclohexene ring of the hound retinoid is innermost, occupying the sarrie position of the phenolic ring of the bound 3,3'-diiorlo-L-tliyrotiitie, whereas the carboxylate group, like the same group of the thyroid hormone, participatcs in an ionic interaction with the LyslS sidc chain at the entrancc of the channel. Despitc the fact that transthyretin was cocrystallized with all-/rrrn,r-retinoic acid, the isoprene chain of the bound retinoid hus bccn found i n a non-exlendcd conforniation. This feature, that allows thc carboxylate to oricnt in a manner suitable for ion-pair association with the LyslS side chain, is attributable to the conversion of all-trans-retinoic acid into cis-isomers or folded cotifortiiers. It is concluded that the prcsence, i n an essentially hydrophobic rnolecular corc of the appropriate s i 7~ 01 a negatively charged group at the correct position is a crucial requirement for Iigand-tratisthyretirl recognition. Whereas the binding of the ligand has no remarkable conscqucnces for the prolein structure, alltmns-retinoic acid undergoes structural changes such as to interact favorably with residues preseni in the thyroxine-binding sites, rcsetiibling roughly the natural ligantl.

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Section: Resultsmentioning

confidence: 61%

Crystal Structure of the Transthyretin–Retinoic‐Acid Complex

Zanotti

D’Acunto

Malpeli

et al. 1995

European Journal of Biochemistry

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“…A transthyretin molecule has extensive fl-sheet structure with monomers having eight p-strands [7]. This characteristic conformation is thought to predispose toward amyloid fibril formation, sometimes causing senile systemic amyloidosis by normal transthyretin in normal-aged individuals [8].…”

Section: Resultsmentioning

confidence: 99%

Identification of a novel transthyretin variant (Val³⁰→Leu) associated with familial amyloidotic polyneuropathy

et al. 1992

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A novel variant transthyretin which contains a leucine‐for‐valine substitution at position 30 was isolated and identified in the serum of a patient with familial amyloidotic polyneuropathy (FAP). The amino acid substitution was proven to result from a guanine‐to‐cytosine change at the first base of codon 30 located in exon 2 in the mutated transthyretin gene by restriction fragment length analysis on the amplified transthyretin gene using Cfr13 I. The study indicates that the point mutation of the transthyretin gene is a cause of the disorder.

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“…A steric interaction has been excluded by X-ray diffraction studies [4] which clearly show that the hormones bind at two discrete and non-overlapping sites within the TTR channel, separated by a distance of 8 A. Ultraccntrifugation [14], circular dichroism [19] and X-ray [9] studies have shown no substantial changes in the conformation of TTR on hormone binding. This has prompted suggestions that the negative cooperativity may be transmitted by a change in the network of hydrogen bonds linking the two non-contiguous sites.…”

Section: Discussionmentioning

confidence: 99%

“…X-Ray crystallography [4,5] has established that two identical binding sites for 1"4 are found in a central channel formed by the association of the four monomers. Two mol of T4 are bound per mol of protein with binding constants two orders of magnitude different for each tool.…”

Section: Introductionmentioning

confidence: 99%

Fluorescence study of the thyroxine‐dependent conformational changes in human serum transthyretin

González

Tapia

1992

FEBS Letters

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Fluorescence studies of transthyretin (TTR) were conducted to detect structural changes associated with the environment of its two tryptophans, induced by binding of thyroxine (T~). Non-radiative tryptophans relaxation rate has an activation energy of 6.4 kcal/mol for TTR, which is decreased to 4.4 Real/reel for TTR-T~ complex. The maximum fl uore~'~nce wavelength was red-shifted as the excitation wavelength was increased. 1"4 changed the magnitude of this shill 1"4 binding per se changed the emission maximum reflecting different environments of the tryptophans. Doublequenching experiments also showed that Ta produces changes in the trl,'ptophans environments. These findings were interpreted as the result of structural alterations in the protein matrix induced by T~ which contribute in part to explain the negative ¢ooperativity associated with the occupancy of the second binding site.

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Structure of human plasma prealbumin at 2.5 A resolution

Cited by 258 publications

References 21 publications

Crystal Structure of the Transthyretin–Retinoic‐Acid Complex

Crystal Structure of the Transthyretin–Retinoic‐Acid Complex

Identification of a novel transthyretin variant (Val³⁰→Leu) associated with familial amyloidotic polyneuropathy

Fluorescence study of the thyroxine‐dependent conformational changes in human serum transthyretin

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Structure of human plasma prealbumin at 2.5 A resolution

Cited by 258 publications

References 21 publications

Crystal Structure of the Transthyretin–Retinoic‐Acid Complex

Crystal Structure of the Transthyretin–Retinoic‐Acid Complex

Identification of a novel transthyretin variant (Val30→Leu) associated with familial amyloidotic polyneuropathy

Fluorescence study of the thyroxine‐dependent conformational changes in human serum transthyretin

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Identification of a novel transthyretin variant (Val³⁰→Leu) associated with familial amyloidotic polyneuropathy