title: The role of disulfide bonds in structure and activity of chlorotoxin.
abstract: BACKGROUND
  Chlorotoxin is a small scorpion peptide that inhibits glioma cell migration. We investigated the importance of a major component of chlorotoxin's chemical structure - four disulfide bonds - to its tertiary structure and biological function.
  
  
  RESULTS
  Five disulfide bond analogs of chlorotoxin were synthesized, with l-α-aminobutyric acid residues replacing each or all of the disulfide bonds. Chemical oxidation and circular dichroism experiments revealed that Cys III-VII and Cys V-VIII were essential for native structure formation. Cys I-IV and Cys II-VI were important for stability of enzymatic proteolysis but not for the inhibition of human umbilical vein endothelial cell migration.
  
  
  CONCLUSIONS
  The disulfide bonds of chlorotoxin are important for its structure and stability and have a minor role in its activity against cell migration.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, QLD, Australia.
authors.forename: Paola G
authors.initials: PG
authors.lastname: Ojeda
authors.forename: Lai Y
authors.initials: LY
authors.lastname: Chan
authors.forename: Aaron G
authors.initials: AG
authors.lastname: Poth
authors.forename: Conan K
authors.initials: CK
authors.lastname: Wang
authors.forename: David J
authors.initials: DJ
authors.lastname: Craik
mesh_terms: D000478:Alkylation; D000595:Amino Acid Sequence; D002465:Cell Movement / Q000187:drug effects; D002942:Circular Dichroism; D003500:Cyclization; D004220:Disulfides / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012604:Scorpion Venoms / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
chemical_list: D004220:Disulfides; D012604:Scorpion Venoms; C091539:Chlorotoxin