• • DRAMP ID

  • DRAMP00877

• • Peptide Name

  • Circulin-A (CIRA; Plant defensin)

• • Source

  • Chassalia parviflora

• • Family

  • Belongs to the cyclotide family

• • Gene

  • Not found

• • Sequence

  • GIPCGESCVWIPCISAALGCSCKNKVCYRN

• • Sequence Length

  • 30

• • UniProt Entry

  • P56871

• • Protein Existence

  • Protein level

• • Biological Activity

  • Antimicrobial, Antibacterial, Anti-Gram+, Anti-Gram-, Antiviral, Antifungal

• • Target Organism

  • • [Ref.10430870]Gram-positive bacterium: Staphylococcus aureus (MIC=0.19 µM).
    • Gram-negative bacterium: Proteus vulgaris (MIC=54.6 µM).
    • Fungi: Candida kefyr (MIC=18.6 µM) and Candida tropicalis (MIC=19.4 µM).
    • NOTE: Medium with 10 mM phosphate buffer.
    • [Ref.18008336]Virus:HIV:inhibition the cytopathic effects of HIV-1 infection in cultured human T-lymphoblast (CEM-SS) cells(EC50=40-260 nM).

• • Hemolytic Activity

  • • [Ref.10430870] EC50 = 1020 μM against blood type A human erythrocytes.

• • Cytotoxicity

  • • [Ref.18008336]CEM-SS cells:IC50=500 nM.

• • Binding Target

  • Not found

• • Linear/Cyclic

  • Cyclic

• • N-terminal Modification

  • Cyclization (N termini to C termini)

• • C-terminal Modification

  • Cyclization (C termini to N termini)

• • Nonterminal Modifications and Unusual Amino Acids

  • [Ref.8920961] There are three disulfide bonds between Cys4 and Cys20, Cys8 and Cys22, Cys13 and Cys27

• • Stereochemistry

  • L

• • Structure

  • Alpha helix (1 helices; 4 residues)

• • Structure Description

  • The molecule is stabilised by three disulfide bonds, two of which form an embedded loop completed by the backbone fragments connecting the cysteine residues. A third disulfide bond threads through the centre of this loop to form a "cystine-knot" motif. This motif is present in a range of other biologically active proteins, including omega-contoxin GVIA and Cucurbita maxima trypsin inhibitor.

• • Helical Wheel Diagram

  • 

• • PDB ID

  • 1BH4 resolved by NMR.

• Predicted Structure

• There is no predicted structure for DRAMP00877.

DRAMP00877

• • Function

  • Probably participates in a plant defense mechanism. Has antibiotic activity. Inhibits the cytopathic effects and replication of the human immunodeficiency virus. Relatively ineffective against Gram-negative bacteria such as E. coli and P. aeruginosa.

• • PTM

  • This is a cyclic peptide which contains three disulfide bonds 1-17; 5-19; 10-24.

• ·Literature 1

• • Title

  • Cyclotides as natural anti-HIV agents.

• • Pubmed ID

  • 18008336

• • Reference

  • Biopolymers. 2008;90(1):51-60. doi: 10.1002/bip.20886.

• • Author

  • Ireland DC, Wang CK, Wilson JA, Gustafson KR, Craik DJ.

• ·Literature 2

• • Title

  • An unusual structural motif of antimicrobial peptides containing end-to-end macrocycle and cystine-knot disulfides.

• • Pubmed ID

  • 10430870

• • Reference

  • Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8913-8918.

• • Author

  • Tam JP, Lu YA, Yang JL, Chiu KW.

• ·Literature 3

• • Title

  • Solution structure by NMR of circulin A: a macrocyclic knotted peptide having anti-HIV activity.

• • Pubmed ID

  • 9878410

• • Reference

  • J. Mol. Biol. 1999; 285:333-345.

• • Author

  • Daly NL, Koltay A, Gustafson KR, Boyd MR, Casas-Finet JR, Craik DJ.

• ·Literature 4

• • Title

  • Analysis of the disulfide linkage pattern in circulin A and B, HIV-inhibitory macrocyclic peptides

• • Pubmed ID

  • 8920961

• • Reference

  • Biochem Biophys Res Commun. 1996 Nov 12;228(2):632-8.

• • Author

  • R Derua 1, K R Gustafson, L K Pannell