The formation of a covalent complex between a dipeptide ligand and the src SH2 domain

Bioorg Med Chem Lett. 1998 May 19;8(10):1189-94. doi: 10.1016/s0960-894x(98)00195-4.

Abstract

The X-ray crystal structure of the src SH2 domain revealed the presence of a thiol residue (Cys 188) located proximal to the phosphotyrosine portion of a dipeptide ligand. An aldehyde bearing ligand (1) was designed to position an electrophilic carbonyl group in the vicinity of the thiol. X-ray crystallographic and NMR examination of the complex formed between (1) and the src SH2 domain revealed a hemithioacetal formed by addition of the thiol to the aldehyde group with an additional stabilizing hydrogen bond between the acetal hydroxyl and a backbone carbonyl.

MeSH terms

  • Aldehydes
  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Cysteine
  • Dipeptides / chemical synthesis
  • Dipeptides / chemistry*
  • Hydrogen Bonding
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Phosphotyrosine
  • Protein Conformation*
  • Proteins / chemistry*
  • src Homology Domains*

Substances

  • Aldehydes
  • Dipeptides
  • Ligands
  • Proteins
  • Phosphotyrosine
  • Cysteine