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Abstract Detail


Protein Modification and Turnover

Craik, David J [1].

Discovery and Applications of the Cyclotides: Circular Knotted Plant Proteins.

The cyclotides [1] are a recently discovered family of plant-derived proteins that have applications in drug design [2] and agriculture [3]. They occur in plants from the Violaceae (violet), Rubiaceae (coffee) and Cucurbitaceae (cucurbit) families and have a diverse range of biological activities, including uterotonic, anti-HIV, antimicrobial, and insecticidal activities, the latter suggesting that their natural function is in plant defence. Individual plants express suites of 10-100 cyclotides at high levels (2g/kg wet plant weight). Cyclotides typically comprise 30 amino acids, contain a head-to-tail cyclised backbone and incorporate three disulfide bonds arranged in a cystine knot topology. In this motif an embedded ring in the structure formed by two disulfide bonds and their connecting backbone segments is penetrated by a third disulfide bond. The combination of this knotted and strongly braced structure with a circular backbone renders the cyclotides impervious to enzymatic breakdown and makes them exceptionally stable. The cyclotides are the largest of several groups of naturally occurring circular proteins that have been discovered over recent years [4]. This presentation will describe the discovery of the cyclotides in plants, their structural characterization, evolutionary relationships and their applications in drug design. Their stability and compact structure makes them an attractive protein framework onto which bioactive peptide epitopes can be grafted to stabilize them.
[1] Craik D J, Cemazar M, Wang C, Daly N L: Biopolymers: Peptide Science 2006, 84, 250
[2] Craik D J, Cemazar M, Daly N L: Curr. Opin. Drug Discovery and Development 2006, 9, 251
[3] Jennings C, West J, Waine C, Craik D, Anderson M. PNAS 2001, 98, 579
[4] Craik D J: Science, 2006, 311, 1561


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Related Links:
cyclotide web site
database on circular proteins


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

Keywords:
cyclotides
host defence peptide
antimicrobial peptide
insecticide
plant-insect interaction
structural biology.

Presentation Type: Plant Biology Abstract
Session: P
Location: Exhibit Hall (Northeast, Southwest & Southeast)/Hilton
Date: Sunday, July 8th, 2007
Time: 8:00 AM
Number: P37003
Abstract ID:174


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