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Information on EC 4.1.1.90 - peptidyl-glutamate 4-carboxylase and Organism(s) Rattus norvegicus and UniProt Accession O88496

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EC Tree
     4 Lyases
         4.1 Carbon-carbon lyases
             4.1.1 Carboxy-lyases
                4.1.1.90 peptidyl-glutamate 4-carboxylase
IUBMB Comments
The enzyme can use various vitamin-K derivatives, including menaquinol, but does not contain iron. The mechanism appears to involve the generation of a strong base by oxygenation of vitamin K. It catalyses the post-translational carboxylation of glutamate residues of several proteins of the blood-clotting system. 9--12 glutamate residues are converted to 4-carboxyglutamate (Gla) in a specific domain of the target protein. The 4-pro-S hydrogen of the glutamate residue is removed and there is an inversion of stereochemistry at this position .
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Rattus norvegicus
UNIPROT: O88496
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The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
carboxylase, matrix gla protein, vitamin k-dependent carboxylase, gamma-glutamyl carboxylase, gamma-carboxylase, vitamin k-dependent gamma-glutamyl carboxylase, vkd carboxylase, glutamate carboxylase, gamma glutamyl carboxylase, vitamin k carboxylase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
gamma-glutamyl carboxylase
-
glutamate carboxylase
-
peptidyl-glutamate 4-carboxylase
-
-
peptidyl-glutamate 4-carboxylase (2-methyl-3-phytyl-1,4-naphthoquinone-epoxidizing)
-
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vitamin K-dependent gamma-glutamyl carboxylase
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-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
peptidyl-4-carboxyglutamate + 2,3-epoxyphylloquinone + H2O = peptidyl-glutamate + CO2 + O2 + phylloquinol
show the reaction diagram
in the physiological process reaction runs in reversed direction
-
SYSTEMATIC NAME
IUBMB Comments
peptidyl-glutamate 4-carboxylase (2-methyl-3-phytyl-1,4-naphthoquinone-epoxidizing)
The enzyme can use various vitamin-K derivatives, including menaquinol, but does not contain iron. The mechanism appears to involve the generation of a strong base by oxygenation of vitamin K. It catalyses the post-translational carboxylation of glutamate residues of several proteins of the blood-clotting system. 9--12 glutamate residues are converted to 4-carboxyglutamate (Gla) in a specific domain of the target protein. The 4-pro-S hydrogen of the glutamate residue is removed [5] and there is an inversion of stereochemistry at this position [6].
CAS REGISTRY NUMBER
COMMENTARY hide
81181-72-8
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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
L-glutamate + CO2 + O2 + vitamin K hydroquinone
gamma-carboxy L-glutamate + vitamin K epoxide + H2O
show the reaction diagram
-
-
-
?
osteocalcin + reduced vitamin K + CO2 + O2
? + vitamin K epoxide + H2O
show the reaction diagram
-
-
-
?
peptidyl-4-carboxyglutamate + 2,3-epoxyphylloquinone + H2O
peptidyl-glutamate + CO2 + O2 + phylloquinone
show the reaction diagram
-
-
-
-
?
peptidyl-L-glutamate + CO2 + O2 + menaquinone
?
show the reaction diagram
-
-
-
-
?
peptidyl-L-glutamate + CO2 + O2 + phylloquinone
peptidyl-4-carboxy L-glutamate + 2,3-epoxyphylloquinone + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
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
L-glutamate + CO2 + O2 + vitamin K hydroquinone
gamma-carboxy L-glutamate + vitamin K epoxide + H2O
show the reaction diagram
-
-
-
?
peptidyl-4-carboxyglutamate + 2,3-epoxyphylloquinone + H2O
peptidyl-glutamate + CO2 + O2 + phylloquinone
show the reaction diagram
-
-
-
-
?
peptidyl-L-glutamate + CO2 + O2 + menaquinone
?
show the reaction diagram
-
-
-
-
?
peptidyl-L-glutamate + CO2 + O2 + phylloquinone
peptidyl-4-carboxy L-glutamate + 2,3-epoxyphylloquinone + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
cis-isomer of vitamin K1, the 2-desmethyl derivative of phylloquinone, MK-1, or menadione (2 -methyl-1,4-naphthoquinone) have little or no activity
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
vitamin K
vitamin K
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-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
Mn2+, high concentrations significantly decrease or have no effect on Km of a peptide substrate for the enzyme
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
iodoacetic acid
poor inhibitor
N-ethylmaleimide
preincubation with vitamin K hydroquinone prevents NEM inhibition of epoxide formation but not of carboxylation
p-chloromercuribenzoate
97% inhibition with 1.25 mM and at 5 mM the reaction is completely inhibited
p-hydroxymercuribenzoate
1 mM, more than 90% inhibition, inhibition is reversed by dithiothreitol
2,3,5,6-Tetrachloro-4-pyridinol
-
TCP, anticoagulant action, effective in vitro inhibitor of the carboxylase
2-chloro-3-phytyl-1,4-naphthoquinone
-
chloro-K, effective in vivo antagonist of vitamin K, inhibits the enzyme in an competitive fashion
5-mercapto-1-methylthiotetrazole
-
-
Boc-Ser(OPO4)-Ser(OPO4)-Leu-OMe
-
inhibits the enzyme apparently competitively with regard to other peptide substrate
CN-
-
enzyme is blocked by mM concentrations of CN-
Cu2+
-
free Cu2+ and Cu2+-complexes inhibit the reaction
ethanol
-
high concentrations
methemoglobin
-
-
-
N-ethylmaleimide
-
-
p-hydroxymercuribenzoate
-
-
additional information
NADH, dithiothreitol, and ATP deficiency decrease enzyme activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
decarboxylated plasma prothrombin
-
activates the enzyme
-
endogenous precursor
-
activates the enzyme
-
N-ethyl-2-(3-methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)tetradecylamide
-
-
additional information
-
enzyme activity increases 2-3fold by a vitamin K deficiency or Warfarin treatment
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2 - 7.4
-
assay at. The activity falls off sharply above pH 8 or below pH 7
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
expression of rat vitamin K-dependent carboxylase in adult and embryonic tissues
Manually annotated by BRENDA team
vitamin K-dependent carboxylase mRNA expression in early rat embryonic development
Manually annotated by BRENDA team
rat hepatoma cell line
Manually annotated by BRENDA team
expression of rat vitamin K-dependent carboxylase in adult and embryonic tissues
Manually annotated by BRENDA team
adult Sprague-Dawley rat
Manually annotated by BRENDA team
expression of rat vitamin K-dependent carboxylase in adult and embryonic tissues
Manually annotated by BRENDA team
expression of rat vitamin K-dependent carboxylase in adult and embryonic tissues
Manually annotated by BRENDA team
expression of rat vitamin K-dependent carboxylase in adult and embryonic tissues
Manually annotated by BRENDA team
expression of rat vitamin K-dependent carboxylase in adult and embryonic tissues
Manually annotated by BRENDA team
expression of rat vitamin K-dependent carboxylase in adult and embryonic tissues
Manually annotated by BRENDA team
expression of rat vitamin K-dependent carboxylase in adult and embryonic tissues
Manually annotated by BRENDA team
expression of rat vitamin K-dependent carboxylase in adult and embryonic tissues
Manually annotated by BRENDA team
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
VKGC_RAT
758
5
87479
Swiss-Prot
other Location (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
85700
calculated from sequence
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
enzyme is not very stable at 37°C and lower temperatures are more desirable. At temperatures below 20°C, extended linear rates of incorporation of 14CO2 into exogenous peptide substrates can be observed
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
difficult, different methods shown
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
in WKY rats receiving a vitamin K-deficient diet that results in a 40% decrease of prothrombin activity, compound N-ethyl-2-(3-methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)tetradecylamide is able to counteract the effects on vitamin K deficiency and results in the complete restoration of prothrombin activity
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Suttie, J.W.
Vitamin K-dependent carboxylase
Annu. Rev. Biochem.
54
459-477
1985
Rattus norvegicus
Manually annotated by BRENDA team
Canfield, L.M.
Vitamin K-dependent oxygenase/carboxylase; differential inactivation by sulfhydryl reagents
Biochem. Biophys. Res. Commun.
148
184-191
1987
Rattus norvegicus (O88496)
Manually annotated by BRENDA team
Romero, E.E.; Deo, R.; Velazquez-Estades, L.J.; Roth, D.A.
Cloning, structural organization, and transcriptional activity of the rat vitamin K-dependent gamma-glutamyl carboxylase gene
Biochem. Biophys. Res. Commun.
248
783-788
1998
Rattus norvegicus (O88496)
Manually annotated by BRENDA team
Helgeland, L.
The submicrosomal site for the conversion of prothrombin precursor to biologically active prothrombin in rat liver
Biochim. Biophys. Acta
499
181-193
1977
Rattus norvegicus (O88496)
Manually annotated by BRENDA team
Romero, E.E.; Velazquez-Estades, L.J.; Deo, R.; Schapiro, B.; Roth, D.A.
Cloning of rat vitamin K-dependent gamma-glutamyl carboxylase and developmentally regulated gene expression in postimplantation embryos
Exp. Cell Res.
243
334-346
1998
Rattus norvegicus (O88496)
Manually annotated by BRENDA team
Kaesler, N.; Schettgen, T.; Mutucumarana, V.P.; Brandenburg, V.; Jahnen-Dechent, W.; Schurgers, L.J.; Krueger, T.
A fluorescent method to determine vitamin K-dependent gamma-glutamyl carboxylase activity
Anal. Biochem.
421
411-416
2012
Rattus norvegicus
Manually annotated by BRENDA team
Vermeer, C.; van t Hoofd, C.; Knapen, M.H.J.; Xanthoulea, S.
Synthesis of 2-methyl-1,4-naphthoquinones with higher gamma-glutamyl carboxylase activity than MK-4 both in vitro and in vivo
Bioorg. Med. Chem. Lett.
27
208-211
2017
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team