Skip to main content
SpringerLink
Log in

Reduced Susceptibility of Moritella profunda Dihydrofolate Reductase to Trimethoprim is Not Due to Glutamate 28

  • Published:
The Protein Journal Aims and scope Submit manuscript

Abstract

The E28D variant of dihydrofolate reductase from Moritella profunda was generated and found to have the same K i (within error) for the competitive inhibitor trimethoprim as the wild type enzyme. Contrary to a previous claim in the literature, Glu 28 is therefore not the cause of the reduced affinity for trimethoprim relative to dihydrofolate reductase from Escherichia coli.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

DHFR:

Dihydrofolate reductase

MpDHFR:

Dihydrofolate reductase from Moritella profunda

EcDHFR:

Dihydrofolate reductase from Escherichia coli

CD:

Circular dichroism

SDS–PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

References

  1. Blakley RL (1960) Nature 188:231–232

    Article  CAS  Google Scholar 

  2. Coque TM, Singh KV, Weinstock GM, Murray BE (1999) Antimicrob Agents Chemother 43:141–147

    Article  CAS  Google Scholar 

  3. Evans RM, Behiry EM, Tey L-H, Guo J, Loveridge EJ, Allemann RK (2010) ChemBioChem 11:2010–2017

    Article  CAS  Google Scholar 

  4. Hay S, Evans RM, Levy C, Loveridge EJ, Wang X, Leys D, Allemann RK, Scrutton NS (2009) ChemBioChem 10:2348–2353

    Article  CAS  Google Scholar 

  5. Hitchings GH, Burchall JJ (1965) Adv Enzymol 27:417–468

    CAS  Google Scholar 

  6. Huovinen P, Sundstrom L, Swedberg G, Skold O (1995) Antimicrob Agents Chemother 39:279–289

    CAS  Google Scholar 

  7. Loveridge EJ, Allemann RK (2011) ChemBioChem 12:1258–1262

    Article  CAS  Google Scholar 

  8. Murakami C, Ohmae E, Tate S, Gekko K, Nakasone K, Kato C (2010) J Biochem 147:591–599

    Article  CAS  Google Scholar 

  9. Sawaya MR, Kraut J (1997) Biochemistry 36:586–603

    Article  CAS  Google Scholar 

  10. Stone SR, Morrison JF (1982) Biochemistry 21:3757–3765

    Article  CAS  Google Scholar 

  11. Stone SR, Morrison JF (1986) Biochim Biophys Acta 869:275–285

    Article  CAS  Google Scholar 

  12. Watson M, Liu JW, Ollis D (2007) FEBS J 274:2661–2671

    Article  CAS  Google Scholar 

  13. Xu Y, Feller G, Gerday C, Glansdorff N (2003) J Bacteriol 185:5519–5526

    Article  CAS  Google Scholar 

  14. Xu Y, Nogi Y, Kato C, Liang ZY, Ruger HJ, De Kegel D, Glansdorff N (2003) Int J Syst Evol Micro 53:533–538

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Funding for this work was provided by the UK. Engineering and Physical Sciences Research Council (Doctoral Training Grant to R.M.E.), the Leonardo da Vinci Programme (A.S.) and Cardiff University.

Author information

Author notes

  1. Rhiannon M. Evans

    Present address: Inorganic Chemistry Laboratory, University of Oxford, Oxford, UK

  2. Anna Sobolewska

    Present address: Manchester Interdisciplinary Biocentre, Faculty of Life Sciences, University of Manchester, Manchester, UK

Authors and Affiliations

  1. School of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT, UK

    E. Joel Loveridge, William M. Dawson, Rhiannon M. Evans, Anna Sobolewska & Rudolf K. Allemann

Authors
  1. E. Joel Loveridge
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William M. Dawson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rhiannon M. Evans
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anna Sobolewska
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rudolf K. Allemann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rudolf K. Allemann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Loveridge, E.J., Dawson, W.M., Evans, R.M. et al. Reduced Susceptibility of Moritella profunda Dihydrofolate Reductase to Trimethoprim is Not Due to Glutamate 28. Protein J 30, 546–548 (2011). https://doi.org/10.1007/s10930-011-9361-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10930-011-9361-x

Keywords

Search

Navigation