A Moecular-model for the Redox Potential Differenc Between Thioredoxin and DSBA, Based on Electostatics Calculations

Gane, Paul J. and Freedman, Robert B. and Warwicker, J. (1995) A Moecular-model for the Redox Potential Differenc Between Thioredoxin and DSBA, Based on Electostatics Calculations. Journal of Molecular Biology, 249 (2). pp. 376-387. ISSN 0022-2836. (The full text of this publication is not available from this repository)

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Official URL
http:dx.doi.org/10.1006/jmbi.1995.0303

Abstract

The disulphide active sites of thioredoxin and DsbA are known to possess a high degree of structural homology: However, DsbA is a much stronger oxidant than thioredoxin. The redox potential difference between DsbA and thioredoxin has been measured to be 160 mV, equivalent to a shift of 15.4 kJ/mol in the reduced/oxidised equilibrium. Electrostatics calculations have been used to study the relative stabilities of the reduced forms of the two proteins. Model calculations suggest that much of the redox potential difference between DsbA and thioredoxin arises form altered stabilisation of the exposed and ionised thiolates of the reduced forms, supporting suggestions previously made on the basis of experimental studies. The calculations have been used to construct a molecular model for the difference in thiolate stabilisation. Although specific interactions, such as thiolate-NH 35 (thioredoxin)/33 (DsbA), provide substantial stabilisation in each reduced protein, the difference between thioredoxin and DsbA is predicted to reside in several side-chain and main-chain groups acting in concert. Residues H32 and Q97 in DsbA are predicted to contribute, along with substantial regions of the polypeptide backbone in the protein domain which is common to DsbA and thioredoxin. Increased thiolate stabilisation by the peptide dipoles is suggested to arise from altered main-chain disposition, and the effect of the additional protein domain of DsbA on the electric field. Peptide dipoles in a region of about 20 residues close to the active site disulphide are predicted to contribute significantly to the redox potential difference.

Item Type: Article
Uncontrolled keywords: REDOX POTENTIAL; PROTEIN ELECTROSTATICS; MOLECULAR MODEL; DISULFIDE FORMATION; PARTIAL CHARGES
Subjects: Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: P. Ogbuji
Date Deposited: 01 Jun 2009 15:36
Last Modified: 16 Jun 2014 14:10
Resource URI: http://kar.kent.ac.uk/id/eprint/19543 (The current URI for this page, for reference purposes)
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