Gamma-glutamyl transpeptidase substrate specificity and catalytic mechanism

Methods Enzymol. 2005;401:449-67. doi: 10.1016/S0076-6879(05)01027-X.

Abstract

The enzyme gamma-glutamyltranspeptidase (GGT) is critical to cellular detoxification and leukotriene biosynthesis processes, as well as amino acid transport in kidneys. GGT has also been implicated in many important physiological disorders, including Parkinson's disease and inhibition of apoptosis. It binds glutathione as donor substrate and initially forms a gamma-glutamyl enzyme that can then react with a water molecule or an acceptor substrate (usually an amino acid or a dipeptide) to form glutamate or a product containing a new gamma-glutamyl isopeptide bond, respectively, thus regenerating the free enzyme. Given the importance of GGT in human physiology, we have undertaken studies of its substrate specificity and catalytic mechanism. In the course of these studies, we have developed methods for the indirect evaluation of donor substrate affinity and stereospecificity and applied others for the measurement of steady state and pre-steady state kinetics and linear free-energy relationships. These methods and the pertinent results obtained with them are presented herein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Animals
  • Binding Sites
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Humans
  • Molecular Conformation
  • Molecular Structure
  • Substrate Specificity
  • gamma-Glutamyltransferase / antagonists & inhibitors
  • gamma-Glutamyltransferase / chemistry
  • gamma-Glutamyltransferase / metabolism*

Substances

  • Enzyme Inhibitors
  • gamma-Glutamyltransferase