4trx
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HIGH-RESOLUTION THREE-DIMENSIONAL STRUCTURE OF REDUCED RECOMBINANT HUMAN THIOREDOXIN IN SOLUTION
OverviewOverview
The solution structure of recombinant human thioredoxin (105 residues) has, been determined by nuclear magnetic resonance (NMR) spectroscopy combined, with hybrid distance geometry-dynamical simulated annealing calculations., Approximate interproton distance restraints were derived from nuclear, Overhauser effect (NOE) measurements. In addition, a large number of, stereospecific assignments for beta-methylene protons and torsion angle, restraints for phi, psi, and chi 1 were obtained by using a conformational, grid search on the basis of the intraresidue and sequential NOE data in, conjunction with 3JHN alpha and 3J alpha beta coupling constants. The, structure calculations were based on 1983 approximate interproton distance, restraints, 52 hydrogen-bonding restraints for 26 hydrogen bonds, and 98, phi, 71 psi, and 72 chi 1 torsion angle restraints. The 33 final simulated, annealing structures obtained had an average atomic rms distribution of, the individual structures about the mean coordinate positions of 0.40 +/-, 0.06 A for the backbone atoms and 0.78 +/- 0.05 A for all atoms. The, solution structure of human thioredoxin consists of a five-stranded, beta-sheet surrounded by four alpha-helices, with an active site, protrusion containing the two redox-active cysteines. The overall, structure is similar to the crystal and NMR structures of oxidized [Katti, S. K., LeMaster, D. M., & Eklund, H. (1990) J. Mol. Biol. 212, 167-184], and reduced [Dyson, J. H., Gippert, G. P., Case, D. A., Holmgren, A., &, Wright, P. (1990) Biochemistry 29, 4129-4136] Escherichia coli, thioredoxin, respectively, despite the moderate 25% amino acid sequence, homology. Several differences, however, can be noted. The human alpha 1, helix is a full turn longer than the corresponding helix in E. coli, thioredoxin and is characterized by a more regular helical geometry. The, helix labeled alpha 3 in human thioredoxin has its counterpart in the, 3(10) helix of the E. coli protein and is also longer in the human, protein. In contrast to these structural differences, the conformation of, the active site loop in both proteins is very similar, reflecting the, perfect sequence identity for a stretch of eight amino acid residues, around the redox-active cysteines.
DiseaseDisease
Known disease associated with this structure: Ciliary dyskinesia, primary, 6 OMIM:[607421]
About this StructureAbout this Structure
4TRX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
High-resolution three-dimensional structure of reduced recombinant human thioredoxin in solution., Forman-Kay JD, Clore GM, Wingfield PT, Gronenborn AM, Biochemistry. 1991 Mar 12;30(10):2685-98. PMID:2001356
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