InterPro domain: IPR010139

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 [ 1 ]. 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.

1. Structural evidence for ammonia tunneling across the (beta alpha)(8) barrel of the imidazole glycerol phosphate synthase bienzyme complex. Structure 10, 185-93