Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary extracted from

  • Lisi, G.P.; East, K.W.; Batista, V.S.; Loria, J.P.
    Altering the allosteric pathway in IGPS suppresses millisecond motions and catalytic activity (2017), Proc. Natl. Acad. Sci. USA, 114, E3414-E3423 .
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
4.3.2.10 drug development the enzyme is a potential therapeutic target absent in mammals but present in bacteria, plants, and fungi. Many plant and human pathogens that infect the immunocompromised patient have an IGPS that is highly homologous to the Saccharomyces cerevisiae and Thermotoga maritima enzymes Thermotoga maritima
4.3.2.10 pharmacology the enzyme is a potential therapeutic target absent in mammals but present in bacteria, plants, and fungi. Many plant and human pathogens that infect the immunocompromised patient have an IGPS that is highly homologous to the Saccharomyces cerevisiae and Thermotoga maritima enzymes Thermotoga maritima

Protein Variants

EC Number Protein Variants Comment Organism
4.3.2.10 D98A HisF subunit mutant, mutation reduces glutaminase activity to 3% compared to activity of wild-type enzyme Thermotoga maritima
4.3.2.10 K19A HisF subunit mutant, mutation reduces glutaminase activity to 3% compared to activity of wild-type enzyme Thermotoga maritima
4.3.2.10 V12A HisF subunit mutant, mutation reduces glutaminase activity to 70% compared to activity of wild-type enzyme Thermotoga maritima
4.3.2.10 V48A HisF subunit mutant, mutation reduces glutaminase activity to 3% compared to activity of wild-type enzyme Thermotoga maritima

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
4.3.2.10 1.4
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme V12A, activated by 1 mM 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide Thermotoga maritima
4.3.2.10 1.74
-
 L-glutamine pH 8.0, 37°C, wild-type enzyme, activated by 1 mM 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide Thermotoga maritima
4.3.2.10 1.99
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme V48A, activated by 1 mM 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide Thermotoga maritima
4.3.2.10 2.88
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme D98A Thermotoga maritima
4.3.2.10 3
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme K19A Thermotoga maritima
4.3.2.10 3.11
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme D98A, activated by 1 mM 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide Thermotoga maritima
4.3.2.10 3.41
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme K19A, activated by 1 mM 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide Thermotoga maritima
4.3.2.10 3.57
-
 L-glutamine pH 8.0, 37°C, wild-type enzyme Thermotoga maritima
4.3.2.10 3.76
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme V48A Thermotoga maritima
4.3.2.10 4.12
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme V12A Thermotoga maritima

Organism

EC Number Organism UniProt Comment Textmining
4.3.2.10 Thermotoga maritima Q9X0C8 and Q9X0C6 Q9X0C8: subunit HisH, Q9X0C6: subunit HisF
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4.3.2.10 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide + NH3 the HisH subunit catalyzes Gln hydrolysis, and the HisF subunit catalyzes the cyclization of the allosteric activator 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide. Ammonia generated in the HisH reaction traverses the dimer interface, where it is used as a substrate in the HisF reaction Thermotoga maritima 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide + D-erythro-1-(imidazol-4-yl)glycerol 3-phosphate + H2O
-
 ?
4.3.2.10 L-glutamine + H2O the HisH subunit catalyzes Gln hydrolysis, and the HisF subunit catalyzes the cyclization of the allosteric activator 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide. Ammonia generated in the HisH reaction traverses the dimer interface, where it is used as a substrate in the HisF reaction Thermotoga maritima L-glutamate + NH3
-
 ?

Synonyms

EC Number Synonyms Comment Organism
4.3.2.10 IGPS
-
 Thermotoga maritima

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
4.3.2.10 0.00165
-
 L-glutamine pH 8.0, 37°C, wild-type enzyme Thermotoga maritima
4.3.2.10 0.00173
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme V12A Thermotoga maritima
4.3.2.10 0.00311
-
 L-glutamine pH 8.0, 37°C, mutant enzyme D98A Thermotoga maritima
4.3.2.10 0.00328
-
 L-glutamine pH 8.0, 37°C, mutant enzyme V48A Thermotoga maritima
4.3.2.10 0.0054
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme K19A Thermotoga maritima
4.3.2.10 0.18
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme D98A, activated by 1 mM 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide Thermotoga maritima
4.3.2.10 0.24
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme V48A, activated by 1 mM 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide Thermotoga maritima
4.3.2.10 0.57
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme K19A, activated by 1 mM 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide Thermotoga maritima
4.3.2.10 1.88
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme V12A, activated by 1 mM 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide Thermotoga maritima
4.3.2.10 3.62
-
 L-glutamine pH 8.0, 37°C, wild-type enzyme, activated by 1 mM 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide Thermotoga maritima

General Information

EC Number General Information Comment Organism
4.3.2.10 malfunction knockouts of IGPS subunit HisF can increase the susceptibility of bacteria to ß-lactam antibiotics and lessen their infectivity Thermotoga maritima

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
4.3.2.10 0.00042
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme V12A Thermotoga maritima
4.3.2.10 0.00046
-
 L-glutamine pH 8.0, 37°C, wild-type enzyme Thermotoga maritima
4.3.2.10 0.00087
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme V48A Thermotoga maritima
4.3.2.10 0.00107
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme D98A Thermotoga maritima
4.3.2.10 0.0018
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme K19A Thermotoga maritima
4.3.2.10 0.0579
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme D98A, activated by 1 mM 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide Thermotoga maritima
4.3.2.10 0.122
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme V48A, activated by 1 mM 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide Thermotoga maritima
4.3.2.10 0.166
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme K19A, activated by 1 mM 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide Thermotoga maritima
4.3.2.10 1.34
-
 L-glutamine pH 8.0, 37°C, HisF mutant enzyme V12A, activated by 1 mM 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide Thermotoga maritima
4.3.2.10 2.08
-
 L-glutamine pH 8.0, 37°C, wild-type enzyme, activated by 1 mM 5-[(5-phospho-1-deoxy-D-ribulos-1-ylamino)methylideneamino]-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide Thermotoga maritima