PDBsum entry 1zd6

Transport protein

PDB id

1zd6

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Contents

			Protein chain

					116 a.a. *

			Metals

					_CL ×6

			Waters ×136

* Residue conservation analysis

PDB id:

1zd6

Links

Name:

Transport protein

Title:

Crystal structure of human transthyretin with bound chloride

Structure:

Transthyretin. Chain: a, b. Synonym: prealbumin, tbpa, ttr, attr. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PDB file)

Resolution:

1.90Å

R-factor:

0.201

R-free:

0.221

Authors:

A.Hornberg,U.W.Hultdin,A.Olofsson,A.E.Sauer-Eriksson

Key ref:

A.Hörnberg et al. (2005). The effect of iodide and chloride on transthyretin structure and stability. Biochemistry, 44, 9290-9299. PubMed id: 15981995 DOI: 10.1021/bi050249z

Date:

14-Apr-05

Release date:

12-Jul-05

PROCHECK

	Headers

	References

Protein chains

P02766 (TTHY_HUMAN) - Transthyretin from Homo sapiens

Seq: Struc:					147 a.a. 116 a.a.

Key:

Secondary structure

CATH domain

DOI no: 10.1021/bi050249z	Biochemistry 44:9290-9299 (2005)
PubMed id: 15981995

The effect of iodide and chloride on transthyretin structure and stability.
A.Hörnberg, U.W.Hultdin, A.Olofsson, A.E.Sauer-Eriksson.

ABSTRACT

Transthyretin amyloid formation occurs through a process of tetramer destabilization and partial unfolding. Small molecules, including the natural ligand thyroxine, stabilize the tetrameric form of the protein, and serve as inhibitors of amyloid formation. Crucial for TTR's ligand-binding properties are its three halogen-binding sites situated at the hormone-binding channel. In this study, we have performed a structural characterization of the binding of two halides, iodide and chloride, to TTR. Chlorides are known to shield charge repulsions at the tetrameric interface of TTR, which improve tetramer stability of the protein. Our study shows that iodides, like chlorides, provide tetramer stabilization in a concentration-dependent manner and at concentrations approximately 15-fold below that of chlorides. To elucidate binding sites of the halides, we took advantage of the anomalous scattering of iodide and used the single-wavelength anomalous dispersion (SAD) method to solve the iodide-bound TTR structure at 1.8 A resolution. The structure of chloride-bound TTR was determined at 1.9 A resolution using difference Fourier techniques. The refined structures showed iodides and chlorides bound at two of the three halogen-binding sites located at the hydrophobic channel. These sites therefore also function as halide-binding sites.

Literature references that cite this PDB file's key reference

PubMed id

Reference

17642520

M.Yogavel, J.Gill, P.C.Mishra, and A.Sharma (2007).
SAD phasing of a structure based on cocrystallized iodides using an in-house Cu Kalpha X-ray source: effects of data redundancy and completeness on structure solution.

Acta Crystallogr D Biol Crystallogr, 63, 931-934.

PDB code:

2q2l

16732734

K.V.Solovyov, A.A.Gasteva, V.V.Egorov, T.D.Aleinikova, A.K.Sirotkin, A.L.Shvartsman, and M.M.Shavlovsky (2006).
Role of the C-terminal fragment of human transthyretin in abnormal fibrillogenesis.

Biochemistry (Mosc), 71, 543-549.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.