1ETB

THE X-RAY CRYSTAL STRUCTURE REFINEMENTS OF NORMAL HUMAN TRANSTHYRETIN AND THE AMYLOIDOGENIC VAL 30-->MET VARIANT TO 1.7 ANGSTROMS RESOLUTION

Summary for 1ETB

• Entry DOI: 10.2210/pdb1etb/pdb
• Descriptor: TRANSTHYRETIN, 3,5,3',5'-TETRAIODO-L-THYRONINE (3 entities in total)
• Functional Keywords: transport(thyroxine)
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P02766
• Total number of polymer chains: 2
• Total formula weight: 29168.51

Authors

Braden, B.C.,Steinrauf, L.K.,Hamilton, J.A. (deposition date: 1993-05-12, release date: 1995-01-26, Last modification date: 2023-11-15)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.7 Å)