ISSN:
0948-5023
Keywords:
Keywords: Thioredoxin
;
Homology modelling
;
Electrostatic potential calculations
;
Protein dipole
;
Force field energies
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Thioredoxin is a small protein (Mr approximately 12,000) found in all living cells from archaebacteria to humans. The active site is highly conserved and has two redox-active cysteine residues in the sequence: -Trp-Cys-Gly-Pro-Cys-. Besides the function of the reduced form as a powerful protein disulfide oxidoreductase, thioredoxin is known to regulate and activate different target enzymes, i.e. ribonucleotide reductase and the mitochondrial 2-oxoacid dehydrogenase multienzyme complexes. Despite the high degree of homology between thioredoxin proteins from different species, there exists a strong variation in the capability of activating target enzymes. This is yet unexplainable, since there still exists no model of a thioredoxin/receptor complex. On the basis of the recently determined amino acid sequence of the thioredoxin Trx2 from rat mitochondria, which is known to be highly efficient in activating mitochondrial 2-oxoacid dehydrogenase multienzyme complexes, we construct the 3-D structure of this protein by homology modelling methods, using the X-ray structures of thioredoxin from E. coli and human as background information. We analyze the differences in the electrostatic properties of the different protein structures and show, that despite the observed homology between the primary sequences, the dipole moment of the protein structures shows significant variations, which might lead to deviations with respect to the binding to the target protein. Using the AMBER 4.0 program package we further investigate and compare the force field energies of the different thioredoxin structures.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s008940050051
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