1TTC

THE X-RAY CRYSTAL STRUCTURE REFINEMENTS OF NORMAL HUMAN TRANSTHYRETIN AND THE AMYLOIDOGENIC VAL30MET VARIANT TO 1.7 ANGSTROMS RESOLUTION

1TTC の概要

• エントリーDOI: 10.2210/pdb1ttc/pdb
• 分子名称: Transthyretin (2 entities in total)
• 機能のキーワード: transport(thyroxine)
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P02766
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27618.85

構造登録者

Hamilton, J.A.,Steinrauf, L.K.,Braden, B.C. (登録日: 1992-11-02, 公開日: 1993-10-31, 最終更新日: 2024-02-14)

主引用文献

Hamilton, J.A.,Steinrauf, L.K.,Braden, B.C.,Liepnieks, J.,Benson, M.D.,Holmgren, G.,Sandgren, O.,Steen, L.
The x-ray crystal structure refinements of normal human transthyretin and the amyloidogenic Val-30-->Met variant to 1.7-A resolution.
J.Biol.Chem., 268:2416-2424, 1993

PubMed Abstract: The x-ray crystal structures of normal human transthyretin (prealbumin) and the amyloidogenic Val-30-Met variant have been refined at 1.7-A resolution to R-values of 0.168 and 0.179, respectively, for 19,882 and 20,362 reflections (Fobs > 2.0 sigma). Standard deviations for stereochemical parameters are 0.018 and 0.022 A for bond distances, 0.030 and 0.038 A for angle distances, and 0.035 and 0.070 A for planar 1-4 distances. The newly refined normal structure shows improvement over the original structure of Blake and Swan (Blake, C. C. F., and Swan, I. D. A. (1971) J. Mol. Biol. 61, 217-224) in stereochemistry and in the conformation of the loop regions. Residues Arg-103, Thr-123, Asn-124, and Pro-125 have now been resolved, and residues 1-9 and 126-127 have been modeled with the aid of simulated annealing refinement. The functional form of transthyretin is a tetramer, having a cylindrical cavity which will bind thyroxine and an exterior binding site for the complex of retinol with retinol-binding protein. The monomer is a beta barrel flattened to become more like a sandwich with residue 30 in the interior. The methionyl for valyl substitution forces the beta sheets of the monomer as much as 1 A apart, resulting in a distortion of the thyroxine-binding cavity, in agreement with the independent observations that the Met-30 variant has low affinity for thyroxine.

PubMed: 8428915

実験手法

X-RAY DIFFRACTION (1.7 Å)