Mechanism of inactivation and identification of sites of modification of ornithine aminotransferase by 4-aminohex-5-ynoate

Biochemistry. 1991 Feb 26;30(8):2239-46. doi: 10.1021/bi00222a029.

Abstract

The inactivation of ornithine aminotransferase by an enzyme-activated irreversible inhibitor 4-aminohex-5-ynoate was accompanied by stoichiometric binding of the radiolabeled compound. Distribution of radiolabel among separated tryptic peptides indicated that more than one amino acid residue had reacted. Lys-292 and Cys-388 were positively identified. Reduction with borohydride was necessary to stabilize the adduct formed with Lys-292, and the relevant peptide prepared after this treatment contained equimolar amounts of inhibitor and coenzyme. The coenzyme chromophore in this peptide showed strong negative circular dichroism. A mechanism consistent with these observations is proposed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / analysis
  • Aminocaproates / metabolism
  • Aminocaproates / pharmacology*
  • Binding Sites
  • Circular Dichroism
  • Kinetics
  • Ornithine-Oxo-Acid Transaminase / antagonists & inhibitors*
  • Peptide Fragments / isolation & purification
  • Protein Binding
  • Protein Denaturation
  • Trypsin
  • Vigabatrin

Substances

  • Amino Acids
  • Aminocaproates
  • Peptide Fragments
  • Ornithine-Oxo-Acid Transaminase
  • Trypsin
  • Vigabatrin