InterPro domain: IPR004651

Histidine is formed by several complex and distinct biochemical reactions catalysed by eight enzymes. Proteins involved in steps 4 and 6 of the histidine biosynthesis pathway are contained in one family. These enzymes are called His6 and His7 in eukaryotes and HisA and HisF in prokaryotes [ 1 , 2 , 3 ]. HisA is a phosphoribosylformimino-5-aminoimidazole carboxamide ribonucleotide isomerase ( 5.3.1.16 ), involved in the fourth step of histidine biosynthesis. The bacterial HisF protein is a cyclase which catalyzes the cyclization reaction that produces D-erythro-imidazole glycerol phosphate during the sixth step of histidine biosynthesis. HisF is also known as imidazole glycerol phosphate synthase [ 4 , 5 , 6 ]. The yeast His7 protein is a bifunctional protein which catalyzes an amido-transferase reaction that generates imidazole-glycerol phosphate and 5-aminoimidazol-4-carboxamide. The latter is the ribonucleotide used for purine biosynthesis. The enzyme also catalyzes the cyclization reaction that produces D-erythro-imidazole glycerol phosphate, and is involved in the fifth and sixth steps in histidine biosynthesis.

This family describes the histidine biosynthesis protein, HisF.

1. Crystal structure of the yeast His6 enzyme suggests a reaction mechanism. Protein Sci. 15, 1516-21
2. The origin and evolution of eucaryal HIS7 genes: from metabolon to bifunctional proteins? Gene 339, 149-60
3. Structure of HisF, a histidine biosynthetic protein from Pyrobaculum aerophilum. Acta Crystallogr. D Biol. Crystallogr. 57, 1518-25
4. Reaction coupling through interdomain contacts in imidazole glycerol phosphate synthase. Biochemistry 44, 11974-85
5. Substrate-induced changes in the ammonia channel for imidazole glycerol phosphate synthase. Biochemistry 42, 7013-22
6. Structure of imidazole glycerol phosphate synthase from Thermus thermophilus HB8: open-closed conformational change and ammonia tunneling. J. Biochem. 132, 759-65