Imidazoleglycerol-phosphate dehydratase explained

imidazoleglycerol-phosphate dehydratase
Ec Number:4.2.1.19
Cas Number:9024-35-5
Go Code:0004424
Width:250
Symbol:IGPD
Imidazoleglycerol-phosphate dehydratase
Pfam:PF00475
Pfam Clan:CL0329
Interpro:IPR000807
Prosite:PDOC00738
Scop:1rhy

The enzyme imidazoleglycerol-phosphate dehydratase catalyzes the chemical reaction

D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate

\rightleftharpoons

3-(imidazol-4-yl)-2-oxopropyl phosphate + H2O

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]

Inhibition

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,, and .[5]

Further reading

Notes and References

  1. Carlomagno MS, Chiariotti L, Alifano P, Nappo AG, Bruni CB . Structure and function of the Salmonella typhimurium and Escherichia coli K-12 histidine operons . J. Mol. Biol. . 203 . 3 . 585–606 . October 1988 . 3062174 . 10.1016/0022-2836(88)90194-5.
  2. Brilli . M. . Fani . R. . 10.1007/s00239-003-2547-x . Molecular Evolution of hisB Genes . Journal of Molecular Evolution . 58 . 2 . 225–237 . 2004 . 15042344. 2004JMolE..58..225B . 1684458 .
  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. 0022-2836. 6990004. 10.1016/0022-2836(80)90377-0.
  4. Book: Cagney. G.. Uetz. P.. Fields. S.. High-throughput screening for protein-protein interactions using two-hybrid assay . 2000. Applications of Chimeric Genes and Hybrid Proteins - Part C: Protein-Protein Interactions and Genomics. Methods in Enzymology. 328. 3–14. 0076-6879. 11075334. 10.1016/s0076-6879(00)28386-9. 9780121822293.
  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 . 1809 - 17 . 16338409. 10.1016/j.str.2005.08.012 . 12 . free .