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110  structures 7166  species 0  interactions 8108  sequences 36  architectures

Family: IGPD (PF00475)

Summary: Imidazoleglycerol-phosphate dehydratase

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This is the Wikipedia entry entitled "Imidazoleglycerol-phosphate dehydratase". More...

Imidazoleglycerol-phosphate dehydratase Edit Wikipedia article

imidazoleglycerol-phosphate dehydratase
EC number4.2.1.19
CAS number9024-35-5
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Imidazoleglycerol-phosphate dehydratase
PDB 1rhy EBI.jpg
crystal structure of imidazole glycerol phosphate dehydratase
Pfam clanCL0329

In enzymology, an imidazoleglycerol-phosphate dehydratase (EC is an enzyme that catalyzes the chemical reaction

D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate 3-(imidazol-4-yl)-2-oxopropyl phosphate + H2O

Hence, this enzyme has one substrate, D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate, and two products, 3-(imidazol-4-yl)-2-oxopropyl phosphate and H2O. This reaction is the sixth step in the biosynthesis of histidine in bacteria, fungi and plants.

This enzyme belongs to the family of lyases, specifically the hydro-lyases, which cleave carbon-oxygen bonds. The systematic name of this enzyme class is D-erythro-1-(imidazol-4-yl)glycerol-3-phosphate hydro-lyase [3-(imidazol-4-yl)-2-oxopropyl-phosphate-forming]. Other names in common use include IGP dehydratase, and D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate hydro-lyase. This enzyme participates in histidine metabolism as it is involved in the 6th step of histidine biosynthesis as part of a nine step cyclical pathway.

There are two isoforms of IGPD; IGPD1 and IGPD2. The different isoforms are highly conserved with only 8 amino acids differing between them. These subtle differences however affect their activity but as yet it is unknown how.

In most organisms IGPD is a monofunctional protein of about 22 to 29 kD. In some bacteria such as Escherichia coli, it is the C-terminal domain of a bifunctional protein that include a histidinol-phosphatase domain.[1] In E. coli, this is the protein encoded by the hisB gene.[2]


Certain compounds that inhibit IGPD have been used as herbicides as animals do not have this protein. One of these inhibitors is 3-Amino-1,2,4-triazole (3-AT), which has also been used as a competitive inhibitor of the product of the yeast HIS3 gene (another IGPD), e.g. in the yeast two-hybrid system.[3][4]

Structural studies

As of late 2007, 3 structures have been solved for this class of enzymes, with PDB accession codes 1RHY, 2AE8, and 2F1D.[5]


  1. ^ Carlomagno MS, Chiariotti L, Alifano P, Nappo AG, Bruni CB (October 1988). "Structure and function of the Salmonella typhimurium and Escherichia coli K-12 histidine operons". J. Mol. Biol. 203 (3): 585–606. doi:10.1016/0022-2836(88)90194-5. PMID 3062174.
  2. ^ Brilli, M.; Fani, R. (2004). "Molecular Evolution of hisB Genes". Journal of Molecular Evolution. 58 (2): 225–237. doi:10.1007/s00239-003-2547-x. PMID 15042344.
  3. ^ Brennan, M. B.; Struhl, K. (1980-01-25). "Mechanisms of increasing expression of a yeast gene in Escherichia coli". Journal of Molecular Biology. 136 (3): 333–338. doi:10.1016/0022-2836(80)90377-0. ISSN 0022-2836. PMID 6990004.
  4. ^ Cagney, G.; Uetz, P.; Fields, S. (2000). "High-throughput screening for protein-protein interactions using two-hybrid assay". Methods in Enzymology. 328: 3–14. doi:10.1016/s0076-6879(00)28386-9. ISSN 0076-6879. PMID 11075334.
  5. ^ Glynn SE, Baker PJ, Sedelnikova SE, Davies CL, Eadsforth TC, Levy CW, Rodgers HF, Blackburn GM, Hawkes TR, Viner R, Rice DW (2005). "Structure and mechanism of imidazoleglycerol-phosphate dehydratase". Structure. 13 (12): 1809–17. doi:10.1016/j.str.2005.08.012. PMID 16338409.

Further reading

  • AMES BN (1957). "The biosynthesis of histidine; D-erythro-imidazoleglycerol phosphate dehydrase". J. Biol. Chem. 228 (1): 131–43. PMID 13475302.

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External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000807

Imidazoleglycerol-phosphate dehydratase (IGPD; EC ) 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 [ PUBMED:16338409 , PUBMED:14724278 , PUBMED:15042344 , PUBMED:10885480 , PUBMED:16511155 , PUBMED:10450980 , PUBMED:8066131 , PUBMED:3001645 , PUBMED:9767718 , PUBMED:8511965 , PUBMED:2664449 , PUBMED:3007936 ].

Gene Ontology

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Domain organisation

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Pfam Clan

This family is a member of clan S5 (CL0329), which has the following description:

This superfamily contains a wide range of families that possess a structure similar to the second domain of ribosomal S5 protein.

The clan contains the following 18 members:

ChlI DNA_gyraseB DNA_mis_repair EFG_IV Fae GalKase_gal_bdg GHMP_kinases_N IGPD Lon_C LpxC Morc6_S5 Ribonuclease_P Ribosomal_S5_C Ribosomal_S9 RNase_PH Topo-VIb_trans UPF0029 Xol-1_N


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Seed source: Prosite
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Finn RD
Number in seed: 489
Number in full: 8108
Average length of the domain: 142.80 aa
Average identity of full alignment: 50 %
Average coverage of the sequence by the domain: 61.02 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.3 20.3
Trusted cut-off 20.9 20.3
Noise cut-off 20.2 19.5
Model length: 144
Family (HMM) version: 20
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Species distribution

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Archea Archea Eukaryota Eukaryota
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Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the IGPD domain has been found. There are 110 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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