Thursday December 15 2005
The 2 Å resolution of a member of this enzyme family from the cyanobacterium Nostoc has shown that the enzyme is a dimer belonging to the cysteine protease family with a conserved catalytic machinery. This system, composed of a catalytic triad and an oxyanion hole, is responsible for the glutathione deglycination step (step 1).
The 1.4 Å resolution of the structure of the enzyme in the presence of its substrate, glutathione, has revealed the existence of an acly-enzyme intermediate (
-glutamyl-cysteine acyl-enzyme) stabilised in a cavity adjacent to a second site of the enzyme that may bind the acceptor molecule required in the second step of the reaction.
Detoxification of heavy metals: first structure of a member of the phytochelatin synthase family
PNAS, (2005) 102: 18848-18853
For the first time, researchers in the Department of Cell Bioenergetics (DEVM, CEA Cadarache) have successfully characterised the structure of a member of the family of phytochelatin synthases (PCS), key enzymes for the detoxification of heavy metals in plants. These results allow a fuller analysis of the catalytic mechanisms of this enzyme family, and help make possible the production of different types of optimised chelating peptides.
The enzyme phytochelatin synthase, a -glutamyl-cysteine transpeptidase, catalyses, from glutathione (-Glu-Cys-Gly), the production of phytochelatins , which are peptides that chelate many heavy metals and favour their sequestration in cell vacuoles.
The catalytic mechanism has two steps:
- Formation of an intermediate -glutamylcysteine acyl-enzyme resulting from the deglycination of glutathione
- Transfer of the -glutamylcysteine unit towards an acceptor molecule (glutathione or phytochelatin).
However, although the two steps in the mechanism of action of this enzyme, which is active only in the presence of heavy metals such as cadmium, are known, no structural information has been available to date.
 |
| Structure of phytochelatin synthase of Nostoc. The enzyme is dimeric; each subunit (one shown as a ribbon and the other as a surface) shows an intermediate -glutamyl cysteine-acyl-enzyme stabilised in the cavity of the active centre. |
The 1.4 Å resolution of the structure of the enzyme in the presence of its substrate, glutathione, has revealed the existence of an acly-enzyme intermediate (
-glutamyl-cysteine acyl-enzyme) stabilised in a cavity adjacent to a second site of the enzyme that may bind the acceptor molecule required in the second step of the reaction.
These findings provide structural support for a fuller understanding of how this family of enzymes functions, and for the production of optimised chelating peptides.