Protein Interactions and Properties Explorer

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  • Protein Properties
  • Center of Mass
  • Disulfide Interactions
  • Ionic Interactions
  • Hydrophobic Interactions
  • Hydrogen Bond Interactions
  • Aromatic-Aromatic Interactions
  • Aromatic-Sulfur Interactions
  • Cation-Pi Interactions

Disulfide Interactions

• A disulfide bond is a covalent bond, usually derived by the coupling of two thiol groups. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore C-S-S-C.
  
  The disulfide bond is strong, a typical bond dissociation energy being 60 kcal/mole. Being about 40% weaker than C-C and C-H bonds, the disulfide bond is thus often the "weak link" in many molecules.
  
  The disulfide bond is about 2.05Å in length, about 0.5Å longer than a C-C bond. Rotation about the S-S axis is subject to a low barrier. Disulfides show a distinct preference for dihedral angles approaching 90°. When the angle approaches 0° or 180°, then the disulfide is a significantly better oxidant.
  
  Disulfide bonds in proteins are formed between the thiol groups of cysteine residues. The other sulfur-containing amino acid, methionine, cannot form disulfide bonds. The prototype of a protein disulfide bond is the two-amino-acid peptide, cystine, which is composed of two cysteine amino acids joined by a disulfide bond (shown in Figure 2 in its unionized form). The structure of a disulfide bond can be described by its ?_ss dihedral angle between the C^� - S^? - S^? - C^� atoms, which is usually close to �90°.
  
  
  
  Cystine is composed of two cysteines linked by a disulfide bond (shown here in its neutral form).
  
  The disulfide bond stabilizes the folded form of a protein in several ways:
  
  

  1) It holds two portions of the protein together, biasing the protein towards the folded topology. Stated differently, the disulfide bond destabilizes the unfolded form of the protein by lowering its entropy.

  2) The disulfide bond may form the nucleus of a hydrophobic core of the folded protein, i.e., local hydrophobic residues may condense around the disulfide bond and onto each other through hydrophobic interactions.

  3) Related to #1 and #2, the disulfide bond link two segments of the protein chain, the disulfide bond increases the effective local concentration of protein residues and lowers the effective local concentration of water molecules. Since water molecules attack amide-amide hydrogen bonds and break up secondary structure, a disulfide bond stabilizes secondary structure in its vicinity. For example, researchers have identified several pairs of peptides that are unstructured in isolation, but adopt stable secondary and tertiary structure upon forming a disulfide bond between them.

Methodology

• Pairs of cysteines (sulphur atoms) within 2.2Å are considered as disulphide bridges.
  
  

  REFERENCES :

  [1] R. J. Cremlyn “An Introduction to Organosulfur Chemistry” John Wiley and Sons: Chichester (1996) ISBN 0 471 95512 4.
  
  [2] Sevier, C. S. and Kaiser, C. A., "Formation and transfer of disulphide bonds in living cells", Nature Reviews Molecular and Cellular Biology, 2002, volume 3, 836-847.
  
  [3] Witt, D., "Recent developments in disulfide bond formation", Synthesis, 2008, 2491-2509. doi:10.1055/s-2008-1067188.
  
  [4] For example the conversion of di-o-nitrophenyl disulfide to o-nitrophenylsulfur chloride Max H. Hubacher (1943). "o-Nitrophenylsulfur chloride". Org. Synth.; Coll. Vol. 2: 455.
  
  [5] Methyl sulfenyl chloride: Irwin B. Douglass and Richard V. Norton (1973). "Methanesulfinyl Chloride". Org. Synth.; Coll. Vol. 5: 709.
  
  [6] Ladenstein, R. and Ren, B., "Reconsideration of an early dogma, saying "there is no evidence for disulfide bonds in proteins from archaea"", Extremophiles, 2008, 12, 29-38.