Award details

Towards the exploitation of IGPD as a target for herbicide development

Reference	BB/C518065/1
Principal Investigator / Supervisor	Professor David Rice
Co-Investigators / Co-Supervisors	Dr Patrick Baker
Institution	University of Sheffield
Department	Molecular Biology and Biotechnology
Funding type	Research
Value (£)	232,619
Status	Completed
Type	Research Grant
Start date	01/10/2005
End date	30/09/2008
Duration	36 months

Abstract

Currently, the market for herbicides is dominated by compounds which act as a limited number of biological targets and the emergence of herbicide resistant weeds is now recognised as a growing problem in agriculture. Sustainable agriculture therefore requires not only the rotation of herbicides that target different modes of action but also, given the current paucity of biological targets, the development of herbicides having novel modes of action. Histidine is an essential dietary nutrient for animals but is synthesized de novo by plants and microorganisms and thus the pathway of histidine biosynthesis is a potential target for herbicide development. Imidazoleglycerol-phosphate dehydratase (IGPD; EC 4.2.1.19) is a metallo enzyme that catalyses the dehydration of imidazoleglycerol phosphate (IGP) to imidazoleacetol phosphate (IAP) and is the seventh step in the pathway for the biosynthesis of histidine. Currently, the mechanism of dehydration is unknown and, with no imine or carbonyl group alpha to the departing proton, must be unusual. The apparent strict requirement for Mn2+ for activity and for assembly of the enzyme to a 24-mer argues strongly for a critical role of the metal in IGPD function. IGPD is the target for a novel class of broad spectrum, phloem-mobile herbicides, the triazole phosphonates, which are thought to act as potent inhibitors on the basis of their close resemblance to a reaction immediate. We have recently obtained crystals of the metal assembled IGPD from Arabidopsis thaliana and in this grant we proposed to determine its molecular structure in the presence and absence of inhibitors to fully define the structure function relationships of this enzyme. In the long term this will provide the underpinning work necessary to fully open up IGPD as a target for rational herbicide discovery.

Summary

unavailable

Committee	Closed Committee - Agri-food (AF)
Research Topics	Crop Science, Plant Science
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	Industrial Partnership Award (IPA)

I accept the terms and conditions of use (opens in new window)

export PDF file

back to list new search