Effects of substitutions in the CXXC active-site motif of the extracytoplasmic thioredoxin ResA

The Biochemical Journal
Allison LewinNick E Le Brun

Abstract

The thiol-disulfide oxidoreductase ResA from Bacillus subtilis fulfils a reductive role in cytochrome c maturation. The pK(a) values for the CEPC (one-letter code) active-site cysteine residues of ResA are unusual for thioredoxin-like proteins in that they are both high (>8) and within 0.5 unit of each other. To determine the contribution of the inter-cysteine dipeptide of ResA to its redox and acid-base properties, three variants (CPPC, CEHC and CPHC) were generated representing a stepwise conversion into the active-site sequence of the high-potential DsbA protein from Escherichia coli. The substitutions resulted in large decreases in the pK(a) values of both the active-site cysteine residues: in CPHC (DsbA-type) ResA, DeltapK(a) values of -2.5 were measured for both cysteine residues. Increases in midpoint reduction potentials were also observed, although these were comparatively small: CPHC (DsbA-type) ResA exhibited an increase of +40 mV compared with the wild-type protein. Unfolding studies revealed that, despite the observed differences in the properties of the reduced proteins, changes in stability were largely confined to the oxidized state. High-resolution structures of two of the variants (CEHC and CPHC ResA) in their...Continue Reading

References

Apr 1, 1968·Journal of Bacteriology·P Fortnagel, E Freese
May 1, 1993·Protein Science : a Publication of the Protein Society·M Wunderlich, R Glockshuber
Dec 15, 1995·Cell·U GrauschopfJ C Bardwell
Apr 8, 1997·Biochemistry·P T ChiversR T Raines
Dec 16, 1997·Biochemistry·P T ChiversR T Raines
Jun 18, 1998·Folding & Design·M Huber-Wunderlich, R Glockshuber
May 30, 1998·Protein Science : a Publication of the Protein Society·E MössnerR Glockshuber
Jun 24, 1998·Biochemistry·G BulajD P Goldenberg
Jun 9, 2000·Molecular Microbiology·N E Le BrunL Hederstedt
Oct 29, 2000·Journal of Bacteriology·M I HutchingsS Spiro
Nov 28, 2000·Acta Crystallographica. Section D, Biological Crystallography·A Vagin, A Teplyakov
Oct 24, 2002·Acta Crystallographica. Section D, Biological Crystallography·Elizabeth PottertonMartin Noble
Feb 22, 2003·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·James W A AllenStuart J Ferguson
Mar 15, 2003·The Journal of Biological Chemistry·Lýğur S ErlendssonNick E Le Brun
Mar 30, 2004·The Journal of Biological Chemistry·Allister CrowArthur Oubrie
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Sep 15, 2006·The Journal of Biological Chemistry·Allison LewinNick E Le Brun
Mar 21, 2007·Journal of Molecular Biology·Goedele RoosJoris Messens
Jul 12, 2007·The Journal of Biological Chemistry·Adele Di MatteoCarlo Travaglini-Allocatelli

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Citations

Jul 7, 2009·Journal of the American Society for Mass Spectrometry·Jonathan T FergusonNeil L Kelleher
Jan 16, 2009·The Journal of Biological Chemistry·Allister CrowLars Hederstedt
Jul 29, 2009·Antioxidants & Redox Signaling·Merridee A WoutersNaomi L Haworth
Feb 9, 2010·Antioxidants & Redox Signaling·Jean-Francois Collet, Joris Messens
Jul 4, 2012·Antioxidants & Redox Signaling·Goedele RoosJoris Messens
May 2, 2013·Acta Crystallographica. Section D, Biological Crystallography·Ji Young YoonSe Won Suh
Aug 14, 2009·PLoS Computational Biology·Goedele RoosJoris Messens
Aug 13, 2013·PloS One·Åsmund Kjendseth RøhrK Kristoffer Andersson
Aug 18, 2009·Molecular Microbiology·Umesh AhujaLars Hederstedt
Jun 25, 2010·Molecular Microbiology·Benjamin J ThompsonMatthew I Hutchings
Oct 1, 2011·The FEBS Journal·Jörg Simon, Lars Hederstedt
Nov 26, 2009·Proteins·S InduRaghavan Varadarajan
Oct 7, 2011·Journal of Signal Transduction·Darío Ortiz de Orué LucanaMatthew R Groves
Feb 27, 2010·Journal of Molecular Biology·Krishan Gopal ThakurB Gopal
Oct 28, 2018·Biological Chemistry·Sérgio F SousaMaria João Ramos
Apr 15, 2017·Applied Microbiology and Biotechnology·Katarzyna M Bocian-OstrzyckaElżbieta Katarzyna Jagusztyn-Krynicka
Dec 7, 2013·The Journal of Biological Chemistry·Lakshmanane PremkumarJennifer L Martin
Jan 17, 2020·International Journal of Biological Macromolecules·Ahmed SayedYu Keung Mok
Mar 7, 2020·International Journal of Biological Macromolecules·Mohamed G AbdelWahedAhmed A Sayed
Feb 18, 2011·Journal of the American Chemical Society·Adriana Badarau, Christopher Dennison

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