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Literature summary for 4.1.1.90 extracted from

  • Mutucumarana, V.P.; Acher, F.; Straight, D.L.; Jin, D.Y.; Stafford, D.W.
    A conserved region of human vitamin K-dependent carboxylase between residues 393 and 404 is important for its interaction with the glutamate substrate (2003), J. Biol. Chem., 278, 46488-46493.
    View publication on PubMed

Protein Variants

Protein Variants Comment Organism
H404A carboxylases W390A, S398A, and H404A have activities similar to that of wild type Homo sapiens
L394R natural mutant, certain individuals with combined deficiencies of vitamin K-dependent proteins have a mutation, L394R, in their gamma-glutamyl carboxylase causing impaired glutamate binding Homo sapiens
additional information Y395A propeptide affinity is similar to that of wild type, but those of L394R and W399A are 16-22fold less than that of wild type. Results of kinetic studies with a propeptide-containing substrate are consistent with results of propeptide binding and FLEEL kinetics. Although propeptide and vitamin K binding in some mutants are affected, our data provide compelling evidence that glutamate recognition is the primary function of the conserved region around Leu394 Homo sapiens
S398A carboxylases W390A, S398A, and H404A have activities similar to that of wild type Homo sapiens
W390A carboxylases W390A, S398A, and H404A have activities similar to that of wild type Homo sapiens
W399A lower activity than wild type Homo sapiens
Y395A lower activity than wild type Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
Boc-(2S,4S)-4-methylglutamic acid-Glu-Val competitive inhibitor, FLEEL as substrate Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.54
-
FLEEL wild type, pH 7.4, 20°C Homo sapiens
6.49
-
FLEEL L394R, pH 7.4, 20°C Homo sapiens
14.8
-
FLEEL Y395A, pH 7.4, 20°C Homo sapiens
24.3
-
FLEEL W399A, pH 7.4, 20°C Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
endoplasmic reticulum rough Homo sapiens 5783
-

Organism

Organism UniProt Comment Textmining
Homo sapiens P38435
-
-

Purification (Commentary)

Purification (Comment) Organism
-
Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
FLEEL + CO2 + O2 + vitamin K hydroquinone
-
Homo sapiens ? + vitamin K epoxide + H2O
-
?
L-glutamate + CO2 + O2 + vitamin K hydroquinone
-
Homo sapiens gamma-carboxy L-glutamate + vitamin K epoxide + H2O
-
?

Synonyms

Synonyms Comment Organism
carboxylase
-
Homo sapiens
gamma-glutamyl carboxylase
-
Homo sapiens
glutamate carboxylase
-
Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
additional information
-
additional information kcat values relative to wild type are 51% (L394R), 1% (Y395A), and 2% (W399A), pH 7.4, 20°C Homo sapiens
0.0019
-
FLEEL Y395A, pH 7.4, 20°C Homo sapiens
0.0033
-
FLEEL W399A, pH 7.4, 20°C Homo sapiens
0.11
-
FLEEL L394R, pH 7.4, 20°C Homo sapiens
0.21
-
FLEEL wild type, pH 7.4, 20°C Homo sapiens

Cofactor

Cofactor Comment Organism Structure
vitamin K conversion of glutamic acid to gamma-carboxyglutamic acid is coupled with the oxygenation of KH2 to vitamin K 2,3-epoxide and has been referred to as vitamin K epoxidase activity Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
additional information Ki value for Boc-(2S,4S)-4-methylglutamic acid-Glu-Val is above 5 mM for W399A, pH 7.4, 20°C Homo sapiens
0.013
-
Boc-(2S,4S)-4-methylglutamic acid-Glu-Val wild type, pH 7.4, 20°C Homo sapiens
1.4
-
Boc-(2S,4S)-4-methylglutamic acid-Glu-Val L394R, pH 7.4, 20°C Homo sapiens
2.1
-
Boc-(2S,4S)-4-methylglutamic acid-Glu-Val Y395A, pH 7.4, 20°C Homo sapiens