NMR as a tool for elucidating the structures of circular and knotted proteins.
Cyclotides are a recently discovered family of mini-proteins that have a head-to-tail cyclised backbone stabilized by a knotted arrangement of three disulfide bonds. They have a wide range of biological activities, including uterotonic, anti-bacterial, anti-HIV, and anti-tumour activity but their insecticidal activities suggest that their natural function is in plant defense. They are exceptionally resistant to chemical, enzymatic and thermal treatments because of their unique structural scaffold. This stability and resistance to proteolysis makes them a potentially valuable protein engineering tool at the interface of chemistry and biology: they have the structure of proteins but the stability and biophysical properties of organic molecules. In this review the role of NMR in defining the structures of cyclotides is described.
Craik
David J
DJ
Institute for Molecular Bioscience and Australian Research Council Special Research Centre for Functional and Applied Genomics, University of Queensland, Brisbane QLD 4072, Australia. d.craik@imb.uq.edu.au
Daly
Norelle L
NL
D000595:Amino Acid Sequence; D047169:Cyclotides / Q000737:chemistry* / Q000378:metabolism; D047168:Cystine Knot Motifs; D008670:Metals / Q000378:metabolism; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship
D047169:Cyclotides; D008670:Metals; D011506:Proteins; C091930:kalata B1; D010767:Phosphorylcholine; C028810:dodecylphosphocholine