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Information on EC 3.5.4.16 - GTP cyclohydrolase I and Organism(s) Neisseria gonorrhoeae and UniProt Accession Q5F9K6

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EC Tree
IUBMB Comments
The reaction involves hydrolysis of two C-N bonds and isomerization of the pentose unit; the recyclization may be non-enzymic. This enzyme is involved in the de novo synthesis of tetrahydrobiopterin from GTP, with the other enzymes involved being EC 1.1.1.153 (sepiapterin reductase) and EC 4.2.3.12 (6-pyruvoyltetrahydropterin synthase) .
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Neisseria gonorrhoeae
UNIPROT: Q5F9K6
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Word Map
The taxonomic range for the selected organisms is: Neisseria gonorrhoeae
The enzyme appears in selected viruses and cellular organisms
Synonyms
gtp cyclohydrolase i, gtpch, gtp cyclohydrolase, gtp cyclohydrolase 1, gtp-ch, gtp-cyclohydrolase i, gch-1, gtpch1, gtpch i, guanosine triphosphate cyclohydrolase i, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
GCYH-IB
GTP cyclohydrolase IB
dihydroneopterin triphosphate synthase
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-
-
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GTP 8-formylhydrolase
-
-
-
-
GTP cyclohydrolase
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-
-
-
guanosine triphosphate 8-deformylase
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-
-
-
guanosine triphosphate cyclohydrolase
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-
-
-
hydrolase, guanosine triphosphate cyclo-
-
-
-
-
Punch protein
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-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
amidine hydrolysis
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-
-
-
SYSTEMATIC NAME
IUBMB Comments
GTP 7,8-8,9-dihydrolase
The reaction involves hydrolysis of two C-N bonds and isomerization of the pentose unit; the recyclization may be non-enzymic. This enzyme is involved in the de novo synthesis of tetrahydrobiopterin from GTP, with the other enzymes involved being EC 1.1.1.153 (sepiapterin reductase) and EC 4.2.3.12 (6-pyruvoyltetrahydropterin synthase) [3].
CAS REGISTRY NUMBER
COMMENTARY hide
37289-19-3
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 7,8-dihydroneopterin 3'-triphosphate
show the reaction diagram
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
GTP + H2O
formate + 7,8-dihydroneopterin 3'-triphosphate
show the reaction diagram
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mn2+
required for activity of isozyme GCYH-1B
Zn2+
Zn2+-dependent enzyme
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
8-oxo-GTP
competitive inhibitor. The inhibitor interacts with a conserved active site Cys149, and this residue is S-nitrosylated. Ki/Km: 0.022
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00915
GTP
pH and temperature not specified in the publication
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000265
GTP
pH and temperature not specified in the publication
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
9.164
2'-deoxy-GTP
pH and temperature not specified in the publication
0.0457
7-deaza-GTP
pH and temperature not specified in the publication
0.000149
8-oxo-GTP
pH and temperature not specified in the publication
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
isozyme GCYH-IB functions to allow folate biosynthesis during Zn2+ starvation
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
108600
isozyme GCYH-1B, apparent molecular weight estimated from gel filtration
135000
gel filtration
28568
4 * 28568, isozyme GCYH-1B, apparent molecular weight estimated from gel filtration
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homotetramer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystals are grown at 20°C by vapor diffusion in sitting drops. High-resolution crystal structures of the enzyme: one in complex with the reaction intermediate analog and competitive inhibitor 8-oxo-GTP, and one with a TRIS molecule bound in the active site and mimicking another reaction intermediate
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C149A
C149S
mutant enzyme exhibits 2.7% of the wild-type activity
E152A
mutant enzyme exhibits about 20% of the wild-type activity
E243A
mutant enzyme exhibits 0.37% of the wild-type activity
H246A
mutant enzyme exhibits 0.74% of the wild-type activity
H246D
mutant enzyme exhibits 3.0% of the wild-type activity
H246K
mutant enzyme shows no activity
H246N
mutant enzyme shows no activity
H246Q
mutant enzyme exhibits 2.4% of the wild-type activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
overexpressed as an N-terminally His6 tagged protein in Bl21(DE3) cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sankaran, B.; Bonnett, S.A.; Shah, K.; Gabriel, S.; Reddy, R.; Schimmel, P.; Rodionov, D.A.; de Crecy-Lagard, V.; Helmann, J.D.; Iwata-Reuyl, D.; Swairjo, M.A.
Zinc-independent folate biosynthesis: genetic, biochemical, and structural investigations reveal new metal dependence for GTP cyclohydrolase IB
J. Bacteriol.
191
6936-6949
2009
Bacillus subtilis, Neisseria gonorrhoeae (Q5F9K6)
Manually annotated by BRENDA team
Paranagama, N.; Bonnett, S.A.; Alvarez, J.; Luthra, A.; Stec, B.; Gustafson, A.; Iwata-Reuyl, D.; Swairjo, M.A.
Mechanism and catalytic strategy of the prokaryotic-specific GTP cyclohydrolase-IB
Biochem. J.
474
1017-1039
2017
Neisseria gonorrhoeae (Q5F9K6), Neisseria gonorrhoeae, Neisseria gonorrhoeae ATCC 700825 (Q5F9K6)
Manually annotated by BRENDA team