Skip to main content

Advertisement

SpringerLink
Log in

Structure of Circulin B and Implications for Antimicrobial Activity of the Cyclotides

  • Published:
International Journal of Peptide Research and Therapeutics Aims and scope Submit manuscript

Abstract

The solution structure of one of the first members of the cyclotide family of macrocyclic peptides to be discovered, circulin B has been determined and compared with that of circulin A and related cyclotides. Cyclotides are mini-proteins derived from plants that have the characteristic features of a head-to-tail cyclised peptide backbone and a knotted arrangement of their three disulfide bonds. First discovered because of their uterotonic or anti-HIV activity, they have also been reported to have activity against a range of Gram positive and Gram negative bacteria as well as fungi. The aim of the current study was to develop structure-activity relationships to rationalise this antimicrobial activity. Comparison of cyclotide structures and activities suggests that the presence and location of cationic residues may be a requirement for activity against Gram negative bacteria. Understanding the topological differences associated with the antimicrobial activity of the cyclotides is of significant interest and potentially may be harnessed for pharmaceutical applications.

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

Similar content being viewed by others

Abbreviations

CCK:

cyclic cystine knot

TOCSY:

2D total correlation spectroscopy

NOE:

nuclear Overhauser effect

NOESY:

2D NOE spectroscopy

DQF-COSY:

double quantum filtered correlation spectroscopy

ECOSY:

exclusive correlation spectroscopy

WATERGATE:

water suppression by gradient-tailored excitation

RMSD:

root mean square deviation

HIV:

human immunodeficiency virus

References

  • D. G. Barry N. L. Daly R. J. Clark L. Sando D. J. Craik (2003) Biochemistry 42 6688–6695

    Google Scholar 

  • D. G. Barry N. L. Daly H. R. Bokesch K. R. Gustafson D. J. Craik (2004) Structure 12 85–94

    Google Scholar 

  • A. Bax D. G. Davis (1985) J. Magn. Reson 65 355–360

    Google Scholar 

  • L. Braunschweiler R. R. Ernst (1983) J. Magn. Reson 53 521–528

    Google Scholar 

  • A. M. Broussalis U. Göransson J. D. Coussio G. Ferraro V. Martino P. Claeson (2001) Phytochemistry 58 47–51

    Google Scholar 

  • A. T. Brünger P. D. Adams L. M. Rice (1997) Structure 5 325–336

    Google Scholar 

  • P. Claeson U. Göransson S. Johansson T. Luijendijk L. Bohlin (1998) J. Nat. Prod 61 77–81

    Google Scholar 

  • G. M. Clore A. T. Brünger M. Karplus A. M. Gronenborn (1986) J. Mol. Biol 191 523–551

    Google Scholar 

  • M. L. Colgrave D. J. Craik (2004) Biochemistry 43 5965–5975

    Google Scholar 

  • D. J. Craik (2001) Toxicon 39 1809–1813

    Google Scholar 

  • D. J. Craik N. L. Daly T. Bond C. Waine (1999) J. Mol. Biol 294 1327–1336

    Google Scholar 

  • D. J. Craik N. L. Daly C. Waine (2001) Toxicon 39 43–60

    Google Scholar 

  • D. J. Craik S. Simonsen N. L. Daly (2002) Curr. Opin. Drug Discov. Devel 5 251–260

    Google Scholar 

  • D. J. Craik N. L. Daly J. Mulvenna M. R. Plan M Trabi (2004) Curr. Prot. Pept. Sci 5 297–315

    Google Scholar 

  • N. L. Daly S. Love P. F. Alewood D. J. Craik (1999a) Biochemistry 38 10606–10614

    Google Scholar 

  • N. L. Daly A. Koltay R. K. Gustafson M. R. Boyd J. R. Casas-Finet D. J. Craik (1999b) J. Mol. Biol 285 333–345

    Google Scholar 

  • R. Derua K. R. Gustafson L. K. Pannell (1996) Biochem. Biophys. Res. Commun 228 632–638

    Google Scholar 

  • Dutton, J. L., Renda, R. F., Waine, C., Clark, R. J., Daly, N. L., Jennings, C. V., Anderson, M. A. and Craik, D. J. 2004, J Biol Chem in press.

  • M. E. Felizmenio-Quimio N. L. Daly D. J. Craik (2001) J. Biol. Chem 276 22875–22882

    Google Scholar 

  • U. Göransson D. J. Craik (2003) J. Biol. Chem 278 48188–48196

    Google Scholar 

  • U. Göransson T. Luijendijk S. Johansson L. Bohlin P. Claeson (1999) J. Nat. Prod 62 283–286

    Google Scholar 

  • L. Gran (1973) Acta Pharmacol. Toxicol 33 400–408

    Google Scholar 

  • C. Griesinger O. W. Sørensen R. R. Ernst (1987) J. Magn. Reson 75 474–492

    Google Scholar 

  • K. R. Gustafson R. C. Sowder SuffixII L. E. Henderson I. C. Parsons Y. Kashman J. H. Cardellina SuffixII J. B. McMahon R. W. Buckheit SuffixJr. L. K. Pannell M. R. Boyd (1994) J. Am. Chem. Soc 116 9337–9338

    Google Scholar 

  • K. R. Gustafson L. K. Walton R. C. Sowder SuffixII D. G. Johnson L. K. Pannell J. H. Cardellina SuffixII M. R. Boyd (2000) J. Nat. Prod 63 176–178

    Google Scholar 

  • R. E. Hancock T. Falla M. Brown (1995) Adv. Microb. Physiol 37 135–75

    Google Scholar 

  • A. Heitz J. F. Hernandez J. Gagnon T. T. Hong T. T. Pham T. M. Nguyen D. Le-Nguyen L. Chiche (2001) Biochemistry 40 7973–7983

    Google Scholar 

  • E. G. Hutchinson J. M. Thornton (1996) Protein Sci. 5 212–220

    Google Scholar 

  • J. Jeener B. H. Meier P. Bachmann R. R. Ernst (1979) J. Chem. Phys 71 4546–4553

    Google Scholar 

  • C. Jennings J. West C. Waine D. Craik M. Anderson (2001) Proc. Natl. Acad. Sci. USA 98 10614–10619

    Google Scholar 

  • R. Koradi M. Billeter K. Wüthrich (1996) J. Mol. Graph 14 29–32

    Google Scholar 

  • R. A. Laskowski J. A. Rullmannn M. W. MacArthur R. Kaptein J. M. Thornton (1996) J. Biomol. NMR 8 477–486

    Google Scholar 

  • J. P. Linge M. Nilges (1999) J. Biomol. NMR 13 51–59

    Google Scholar 

  • D. Marion K. Wüthrich (1983) Biochem. Biophys. Res. Commun 113 967–974

    Google Scholar 

  • P. K. Pallaghy K. J. Nielsen D. J. Craik R. S. Norton (1994) Protein Sci 3 1833–1839

    Google Scholar 

  • M. Piotto V. Saudek V. Sklenar (1992) J. Biomol. NMR 2 661–665

    Google Scholar 

  • M. Rance O. W. Sørensen G. Bodenhausen G. Wagner R. R. Ernst K. Wüthrich (1983) Biochem. Biophys. Res. Commun 117 479–485

    Google Scholar 

  • K. J. Rosengren N. L. Daly M. R. Plan C. Waine D. J. Craik (2003) J. Biol. Chem 278 8606–8616

    Google Scholar 

  • O. Saether D. J. Craik I. D. Campbell K. Sletten J. Juul D. G. Norman (1995) Biochemistry 34 4147–4158

    Google Scholar 

  • T. Schöpke M. I. Hasan Agha R. Kraft A. Otto K. Hiller (1993) Sci. Pharm 61 145–153

    Google Scholar 

  • J. P. Tam Y-A. Lu (1997) Tetrahedron Lett 38 5599–5602

    Google Scholar 

  • J. P. Tam Y. A. Lu J. L. Yang K. W. Chiu (1999) Proc. Natl. Acad. Sci. USA 96 8913–8918

    Google Scholar 

  • M. Trabi D. J. Craik (2002) Trends Biochem. Sci 27 132–138

    Google Scholar 

  • M. Trabi D. J. Craik (2004) Plant Cell 16 2204–2216

    Google Scholar 

  • C. G. Wilde J. E. Griffith M. N. Marra J. L. Snable R. W. Scott (1989) J. Biol. Chem 264 11200–11203

    Google Scholar 

  • M. P. Williamson T. F. Havel K. Wüthrich (1985) J. Mol. Biol 182 295–315

    Google Scholar 

  • K. M. Witherup M. J. Bogusky P. S. Anderson H. Ramjit R. W. Ransom T. Wood M. Sardana (1994) J. Nat. Prod 57 1619–1625

    Google Scholar 

  • K. Wüthrich (1986) NMR of Proteins and Nucleic Acids Wiley-Interscience New York

    Google Scholar 

  • K. Wüthrich M. Billeter W. Braun (1983) J. Mol. Biol 169 949–961

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, 4072, Australia

    Anita Koltay, Norelle L. Daly & David J. Craik

  2. Molecular Targets Development Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA

    Kirk R. Gustafson

Authors
  1. Anita Koltay
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Norelle L. Daly
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kirk R. Gustafson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David J. Craik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David J. Craik.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koltay, A., Daly, N.L., Gustafson, K.R. et al. Structure of Circulin B and Implications for Antimicrobial Activity of the Cyclotides. Int J Pept Res Ther 11, 99–106 (2005). https://doi.org/10.1007/s10989-004-1722-2

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10989-004-1722-2

Key words

Search

Navigation