4.3.1.B2	L-glutamine + H2O	the enzyme constitutes a bienzyme complex of the glutaminase subunit HisH and the synthase subunit HisF. Nascent ammonia produced by HisH reacts at the active site of HisF with N'-((5'-phosphoribulosyl)formimino)-5-aminoimidazole-4-carboxamide-ribonucleotide to yield the products imidazoleglycerol phosphate and 5-aminoimidazole-4-carboxamide ribotide. Isolated subunit HisH shows no detectable glutaminase activity but is stimulated by complex formation with subunit HisF to which either the product imidazole glycerol phosphate or a substrate analogue are bound	Thermotoga maritima	L-glutamate + NH3	-	?	116389	
4.3.1.B2	L-glutamine + H2O	the enzyme constitutes a bienzyme complex of the glutaminase subunit HisH and the synthase subunit HisF. Nascent ammonia produced by HisH reacts at the active site of HisF with N'-((5'-phosphoribulosyl)formimino)-5-aminoimidazole-4-carboxamide-ribonucleotide to yield the products imidazoleglycerol phosphate and 5-aminoimidazole-4-carboxamide ribotide. Isolated subunit HisH shows no detectable glutaminase activity but is stimulated by complex formation with subunit HisF to which either the product imidazole glycerol phosphate or a substrate analogue are bound	Thermotoga maritima DSM 3109	L-glutamate + NH3	-	?	116389	
4.3.1.B2	L-glutamine + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-monophosphate	the enzyme catalyzes two different reactions at two separate active sites. At the glutaminase active site, glutamine is hydrolyzed to glutamate and ammonia, which, at the synthase active site, reacts with the acceptor substrate N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-monophosphate. Ammonia is channeled between glutaminase and synthase active sites	Thermotoga maritima	L-glutamate + D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	428725	
4.3.1.B2	L-glutamine + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-monophosphate	the enzyme constitutes a bienzyme complex of the glutaminase subunit HisH and the synthase subunit HisF. Nascent ammonia produced by HisH reacts at the active site of HisF with N'-((5'-phosphoribulosyl)formimino)-5-aminoimidazole-4-carboxamide-ribonucleotide to yield the products imidazole glycerol phosphate and 5-aminoimidazole-4-carboxamide ribotide. Isolated subunit HisH shows no detectable glutaminase activity but is stimulated by complex formation with subunit HisF to which either the product imidazole glycerol phosphate or a substrate analogue are bound	Thermotoga maritima	L-glutamate + D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	428725	
4.3.1.B2	L-glutamine + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-monophosphate	the enzyme catalyzes two different reactions at two separate active sites. At the glutaminase active site, glutamine is hydrolyzed to glutamate and ammonia, which, at the synthase active site, reacts with the acceptor substrate N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-monophosphate. Ammonia is channeled between glutaminase and synthase active sites	Thermotoga maritima DSM 3109	L-glutamate + D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	428725	
4.3.1.B2	L-glutamine + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-monophosphate	the enzyme constitutes a bienzyme complex of the glutaminase subunit HisH and the synthase subunit HisF. Nascent ammonia produced by HisH reacts at the active site of HisF with N'-((5'-phosphoribulosyl)formimino)-5-aminoimidazole-4-carboxamide-ribonucleotide to yield the products imidazole glycerol phosphate and 5-aminoimidazole-4-carboxamide ribotide. Isolated subunit HisH shows no detectable glutaminase activity but is stimulated by complex formation with subunit HisF to which either the product imidazole glycerol phosphate or a substrate analogue are bound	Thermotoga maritima DSM 3109	L-glutamate + D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	428725	
4.3.1.B2	L-glutamine + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate	-	Thermus thermophilus	L-glutamate + D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	427463	
4.3.1.B2	L-glutamine + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate	-	Thermotoga maritima	L-glutamate + D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	427463	
4.3.1.B2	L-glutamine + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate	-	Saccharomyces cerevisiae	L-glutamate + D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	427463	
4.3.1.B2	L-glutamine + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate	-	Escherichia coli	L-glutamate + D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	427463	
4.3.1.B2	L-glutamine + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate	the enzyme catalyzes a step in the histidine biosynthetic pathway located at the branch point to de novo purine biosynthesis	Thermus thermophilus	L-glutamate + D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	427463	
4.3.1.B2	L-glutamine + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate	the imidazole glycerol phosphate synthase catalyzes formation of the imidazole ring in histidine biosynthesis	Saccharomyces cerevisiae	L-glutamate + D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	427463	
4.3.1.B2	L-glutamine + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate	the enzyme is also a glutamine amidotransferase, which produces ammonia in a glutaminase active site and channels it through a 30 A internal tunnel to a cyclase active site	Saccharomyces cerevisiae	L-glutamate + D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	427463	
4.3.1.B2	L-glutamine + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate	-	Thermus thermophilus HB8 / ATCC 27634 / DSM 579	L-glutamate + D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	427463	
4.3.1.B2	L-glutamine + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate	the enzyme catalyzes a step in the histidine biosynthetic pathway located at the branch point to de novo purine biosynthesis	Thermus thermophilus HB8 / ATCC 27634 / DSM 579	L-glutamate + D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	427463	
4.3.1.B2	L-glutamine + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate	-	Saccharomyces cerevisiae	L-glutamate + D-erythro-imidazole-glycerol-phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	428726	
4.3.1.B2	additional information	the enzyme also shows glutaminase activity. The glutaminase activity of the glutaminase domain is tightly regulated by the acceptor substrate domain. In IGP synthase the glutaminase and N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate binding sites are separated by 30 A. Using kinetic analyses of site-specific mutants and molecular dynamic simulations, it is determined that an interdomain salt bridge in IGP synthase between D359 and K196 (approximately 16 A from the N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate binding site) plays a key role in mediating communication between the two active sites. This interdomain contact modulates the glutaminase loop containing the histidine and glutamic acid of the catalytic triad to control glutamine hydrolysis	Saccharomyces cerevisiae	?	-	?	89	
4.3.1.B2	additional information	the enzyme shows a low basal level glutaminase activity that can be enhanced 1000fold in the presence of a nucleotide substrate or analog	Saccharomyces cerevisiae	?	-	?	89	
4.3.1.B2	additional information	the glutaminase activity for the holoenzyme is 0.8% of that in the presence of the nucleotide substrate N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate	Escherichia coli	?	-	?	89	
4.3.1.B2	additional information	the glutaminase activity of the enzyme is stimulated 4900fold in the presence of the acceptor substrate N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate	Saccharomyces cerevisiae	?	-	?	89	
4.3.1.B2	N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate + L-glutamine	for the IGP synthase holoenzyme L-glutamine is a more efficient substrate relative to ammonium ion by a factor of 1000. The HisF subunit alone does not ulilize L-glutamine. It supports an ammonia-dependent reaction with a turnover number similar to that of the holoenzyme with glutamine	Escherichia coli	L-glutamate + D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	D-erythro-1-(imidazol-4-yl)glycerol phosphate i.e. (2R,3S)-2,3-dihydroxy-3-(1H-imidazol-4-yl)propyl phosphate. 5-Amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide i.e. [(2R,3S,4R,5R)-5-(4-carbamoyl-5-aminoimidazol-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate i.e. AICAR	?	427490	
4.3.1.B2	N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate + NH3	the protein encoded by the hisF gene has an ammonia-dependent activity, it does not utilize L-glutamine as substrate. The ammonia-dependent reaction is completely independent of the HisH protein	Escherichia coli	D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	D-erythro-1-(imidazol-4-yl)glycerol phosphate i.e. (2R,3S)-2,3-dihydroxy-3-(1H-imidazol-4-yl)propyl phosphate. 5-Amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide i.e. [(2R,3S,4R,5R)-5-(4-carbamoyl-5-aminoimidazol-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate i.e. AICAR	?	428818	
4.3.1.B2	N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate + NH3	the enzyme constitutes a bienzyme complex of the glutaminase subunit HisH and the synthase subunit HisF. Nascent ammonia produced by HisH reacts at the active site of HisF with N'-((5'-phosphoribulosyl)formimino)-5-aminoimidazole-4-carboxamide-ribonucleotide to yield the products imidazole glycerol phosphate and 5-aminoimidazole-4-carboxamide ribotide. Isolated subunit HisH shows no detectable glutaminase activity but is stimulated by complex formation with subunit HisF to which either the product imidazole glycerol phosphate or a substrate analogue are bound	Thermotoga maritima	D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	428818	
4.3.1.B2	N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate + NH3	the enzyme constitutes a bienzyme complex of the glutaminase subunit HisH and the synthase subunit HisF. Nascent ammonia produced by HisH reacts at the active site of HisF with N'-((5'-phosphoribulosyl)formimino)-5-aminoimidazole-4-carboxamide-ribonucleotide to yield the products imidazole glycerol phosphate and 5-aminoimidazole-4-carboxamide ribotide. Isolated subunit HisH shows no detectable glutaminase activity but is stimulated by complex formation with subunit HisF to which either the product imidazole glycerol phosphate or a substrate analogue are bound	Thermotoga maritima DSM 3109	D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	428818	
4.3.1.B2	N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate + NH4+	the protein encoded by the hisF gene has an ammonia-dependent activity, it does not utilize L-glutamine as substrate. The ammonia-dependent reaction is completely independent of the HisH protein	Escherichia coli	D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	D-erythro-1-(imidazol-4-yl)glycerol phosphate i.e. (2R,3S)-2,3-dihydroxy-3-(1H-imidazol-4-yl)propyl phosphate. 5-Amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide i.e. [(2R,3S,4R,5R)-5-(4-carbamoyl-5-aminoimidazol-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate i.e. AICAR	?	428819	
4.3.1.B2	NH4+ + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate	-	Thermotoga maritima	D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	428838	
4.3.1.B2	NH4+ + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate	-	Saccharomyces cerevisiae	D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	428838	
4.3.1.B2	NH4+ + N1-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamido-1-beta-D-ribofuranosyl 5'-phosphate	-	Escherichia coli	D-erythro-1-(imidazol-4-yl)glycerol phosphate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide	-	?	428838