Peptide name : Varv peptide F (Varv F; Plant defensin)

Source/Organism : Field pansy

Linear/Cyclic : Cyclic

Chirality : L

Peptide length: 29

C-terminal modification: Cyclic

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Not specified

Assay time : Not found

Activity : IC50 : > 10 µg/mL

Cell line : BEL-7402

Cancer type : Not found

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 2983.4229 Dalton

Aliphatic index : 0.503

Instability index : 52.4621

Hydrophobicity (GRAVY) : 0.3414

Isoelectric point : 5.9618

Charge (pH 7) : -0.2975

Aromaticity : 0.069

Molar extinction coefficient (cysteine, cystine): (6990, 7365)

Hydrophobic/hydrophilic ratio : 1.63636363

hydrophobic moment : 0.2507

Missing amino acid : H,Q,M,K,F,D

Most occurring amino acid : C

Most occurring amino acid frequency : 6

Least occurring amino acid : I

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.1, 0.3, 0.3)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)CN)C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(=O)O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O

1 : Wang CK, et al. Combined X-ray and NMR analysis of the stability of the cyclotide cystine knot fold that underpins its insecticidal activity and potential use as a drug scaffold. J Biol Chem. 2009; 284:10672-83. doi: 10.1074/jbc.M900021200

Paper title : Combined X-ray and NMR analysis of the stability of the cyclotide cystine knot fold that underpins its insecticidal activity and potential use as a drug scaffold.

Doi : https://doi.org/10.1074/jbc.M900021200

Abstract : Cyclotides are a family of plant defense proteins that are highly resistant to adverse chemical, thermal, and enzymatic treatment. Here, we present the first crystal structure of a cyclotide, varv F, from the European field pansy, Viola arvensis, determined at a resolution of 1.8 A. The solution state NMR structure was also determined and, combined with measurements of biophysical parameters for several cyclotides, provided an insight into the structural features that account for the remarkable stability of the cyclotide family. The x-ray data confirm the cystine knot topology and the circular backbone, and delineate a conserved network of hydrogen bonds that contribute to the stability of the cyclotide fold. The structural role of a highly conserved Glu residue that has been shown to regulate cyclotide function was also determined, verifying its involvement in a stabilizing hydrogen bond network. We also demonstrate that varv F binds to dodecylphosphocholine micelles, defining the binding orientation and showing that its structure remains unchanged upon binding, further demonstrating that the cyclotide fold is rigid. This study provides a biological insight into the mechanism by which cyclotides maintain their native activity in the unfavorable environment of predator insect guts. It also provides a structural basis for explaining how a cluster of residues important for bioactivity may be involved in self-association interactions in membranes. As well as being important for their bioactivity, the structural rigidity of cyclotides makes them very suitable as a stable template for peptide-based drug design.