Imidazoleglycerol-phosphate dehydratase (IGPD; EC 4.2.1.19) catalyzes the dehydration of imidazole glycerol phosphate to imidazole acetol phosphate, the sixth step of histidine biosynthesis in plants and microorganisms where the histidine is synthesized de novo. There is an internal repeat in the protein domain that is related by pseudo-dyad symmetry, perhaps as a result of an ancient gene duplication. The apo-form of IGPD exists as a catalytically inactive trimer which, in the presence of specific divalent metal cations such as manganese (Mn2+), cobalt (Co2+), cadmium (Cd2+), nickel (Ni2+), iron (Fe2+) and zinc (Zn2+), assembles to form a biologically active high molecular weight metalloenzyme; a 24-mer with 4-3-2 symmetry. Each 24-mer has 24 active sites, and contains around 1.5 metal ions per monomer, each monomer contributing residues to three separate active sites. IGPD enzymes are monofunctional in fungi, plants, archaea and some eubacteria while they are encoded as bifunctional enzymes in other eubacteria, such that the enzyme is fused to histidinol-phosphate phosphatase, the penultimate enzyme of the histidine biosynthesis pathway. The histidine biosynthesis pathway is a potential target for development of herbicides, and IGPD is a target for the triazole phosphonate herbicides.
Feature 1:putative active site pocket [active site]
Evidence:
Comment:These active site residues are inferred from manual docking experiments where the putative diazafulvene intermediate is docked into the metal-binding cavity.
Comment:IGPD is inactive as a trimer. In the presence of divalent cations, it assembles into an active 24-mer with 4-3-2 symmetry, and 24 active sites. Within the assembled enzyme, each monomer contributes residues to three separate active sites.
Structure:2F1D_D/G/H: Arabidopsis thaliana IGPD, showing one active site involving three subunits bound with two manganese ions and a sulfate ion; contact distance at 4A.
Comment:The sulfate ion represents the substrate's phosphate moiety.
Comment:Two trimers participate at each active site. One trimer contributes residues from two subunits and the other trimer contributes residues from a single subunit.
Structure:2F1D: Arabidopsis thaliana IGPD, showing a monomer contributing residues to three active sites; contact distance at 4A.
Jiyao W et al.(2023). "The conserved domain database in 2023.",