InterPro domain: IPR000807

Imidazoleglycerol-phosphate dehydratase (IGPD; 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 [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ].

1. Structure and mechanism of imidazoleglycerol-phosphate dehydratase. Structure 13, 1809-17
2. Crystal structure of imidazole glycerol-phosphate dehydratase: duplication of an unusual fold. J. Biol. Chem. 279, 15491-8
3. Molecular evolution of hisB genes. J. Mol. Evol. 58, 225-37
4. Oxo-vanadium as a spin probe for the investigation of the metal coordination environment of imidazole glycerol phosphate dehydratase. J. Inorg. Biochem. 80, 161-8
5. Purification, crystallization and preliminary crystallographic analysis of Arabidopsis thaliana imidazoleglycerol-phosphate dehydratase. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 61, 776-8
6. Design and synthesis of beta-carboxamido phosphonates as potent inhibitors of imidazole glycerol phosphate dehydratase. Bioorg. Med. Chem. Lett. 9, 2053-8
7. Isolation and characterization of cDNAs encoding imidazoleglycerolphosphate dehydratase from Arabidopsis thaliana. Plant Physiol. 105, 579-83
8. Nucleotide sequence and transcriptional mapping of the yeast pet56-his3-ded1 gene region. Nucleic Acids Res. 13, 8587-601
9. Buchnera aphidicola (Aphid endosymbiont) contains genes encoding enzymes of histidine biosynthesis. Curr. Microbiol. 37, 356-8
10. Molecular genetics in Saccharomyces kluyveri: the HIS3 homolog and its use as a selectable marker gene in S. kluyveri and Saccharomyces cerevisiae. Yeast 9, 351-61
11. Cloning of histidine genes of Azospirillum brasilense: organization of the ABFH gene cluster and nucleotide sequence of the hisB gene. Mol. Gen. Genet. 216, 224-9
12. Gene structure in the histidine operon of Escherichia coli. Identification and nucleotide sequence of the hisB gene. Mol. Gen. Genet. 202, 42-7