Imidazole glycerol phosphate synthase, subunit H (IPR010139)

Short name: Imidazole-glycPsynth_HisH

Overlapping homologous superfamilies

Family relationships



Imidazole glycerol phosphate synthetase (IGPS) is a key metabolic enzyme, which links amino acid and nucleotide biosynthesis: it catalyses the closure of the imidazole ring within histidine biosynthesis (fifth step), and provides the substrate for de novo purine biosynthesis. IGPS consists of two different subunits: HisH, a glutamine amidotransferase (glutaminase), and HisF, a synthase (cyclase). HisH functions to provide a source of nitrogen, which is required for the synthesis of histidine and purines. In the HisH glutaminase reaction, the hydrolysis of glutamine yields ammonia, which is then used by HisF in the subsequent synthase reaction. The X-ray structure of the HisH/HisF heterodimer of IGPS reveals a putative tunnel for the transfer of ammonia from HisH to HisF via a (beta-alpha)8 barrel fold within HisF that abuts HisH [PMID: 11839304]. Ammonia tunnels connect the glutaminase and synthase active sites.

HisH belongs to a large group of enzymes found in diverse and fundamental anabolic pathways. These enzymes share a common domain, referred to as the type-I glutamine amidotransferase (GATase) domain, which can occur either as single polypeptides (as with HisH) or as domains of large multifunctional proteins.

GO terms

Biological Process

GO:0000105 histidine biosynthetic process

Molecular Function

GO:0016763 transferase activity, transferring pentosyl groups

Cellular Component

GO:0005737 cytoplasm

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.