EC - Peptidyl-glutamate 4-carboxylase

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IntEnz Enzyme Nomenclature


Accepted name:
peptidyl-glutamate 4-carboxylase
Other names:
vitamin K-dependent carboxylase
γ-glutamyl carboxylase
peptidyl-glutamate 4-carboxylase (2-methyl-3-phytyl-1,4-naphthoquinone-epoxidizing)
Systematic name:
peptidyl-glutamate 4-carboxylase (2-methyl-3-phytyl-1,4-naphthoquinol-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].

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , DIAGRAM , DIAGRAM , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Structural data: CSA , EC2PDB


  1. Dowd, P., Hershline, R., Ham, S. W., Naganathan, S.
    Vitamin K and energy transduction: a base strength amplification mechanism.
    Science 269: 1684-1691 (1995). [PMID: 7569894]
  2. Furie, B., Bouchard, B. A., Furie, B. C.
    Vitamin K-dependent biosynthesis of γ-carboxyglutamic acid.
    Blood 93: 1798-1808 (1999). [PMID: 10068650]
  3. Rishavy, M. A., Hallgren, K. W., Yakubenko, A. V., Shtofman, R. L., Runge, K. W., Berkner, K. L.
    Bronsted analysis reveals Lys218 as the carboxylase active site base that deprotonates vitamin K hydroquinone to initiate vitamin K-dependent protein carboxylation.
    Biochemistry 45: 13239-13248 (2006). [PMID: 17073445]
  4. Silva, P. J., Ramos, M. J.
    Reaction mechanism of the vitamin K-dependent glutamate carboxylase: a computational study.
    The journal of physical chemistry. B 111: 12883-12887 (2007). [PMID: 17935315]
  5. Decottignies-Le Marechal, P., Ducrocq, C., Marquet, A., Azerad, R.
    The stereochemistry of hydrogen abstraction in vitamin K-dependent carboxylation.
    J. Biol. Chem. 259: 15010-15012 (1984). [PMID: 6150930]
  6. Dubois, J., Dugave, C., Foures, C., Kaminsky, M., Tabet, J. C., Bory, S., Gaudry, M., Marquet, A.
    Vitamin K dependent carboxylation: determination of the stereochemical course using 4-fluoroglutamyl-containing substrate.
    Biochemistry 30: 10506-10512 (1991). [PMID: 1931973]
  7. Rishavy, M. A., Berkner, K. L.
    Vitamin K oxygenation, glutamate carboxylation, and processivity: defining the three critical facets of catalysis by the vitamin K-dependent carboxylase.
    Adv Nutr 3: 135-148 (2012). [PMID: 22516721]

[EC created 2009]